BR112019008056B1 - Source of electromagnetic radiation and multi-phase oral composition for use in oral care - Google Patents

Abstract

The present invention relates to a multi-phase oral composition and a source of electromagnetic radiation for teeth whitening.

Description

FIELD OF THE INVENTION

[0001] The present invention relates to multi-phase oral compositions and a source of electromagnetic radiation for teeth whitening.

BACKGROUND OF THE INVENTION

[0002] Currently, there are dental products on the market through which various cosmetic and/or therapeutic active ingredients are applied to the teeth and oral cavity. Examples of these products include: brushing aids such as toothpaste products to release active ingredients for oral care, eg polyphosphates or fluorides; mouthwashes containing breath fresheners or antibacterial active ingredients; and whitening tapes for applying active whitening ingredients to teeth. In particular, the use of a dental tape has been recognized as a convenient and inexpensive way to provide cosmetic and therapeutic benefits to teeth and to the mucosal surfaces of the oral cavity; for example, tooth whitening tapes, where a whitening composition is applied to a tape and then applied to the teeth to achieve sustained contact between the teeth and the whitening composition.

[0003]Despite the above known approaches to treating oral health issues, especially for teeth whitening, there is still a need to provide products with improved whitening efficacy, faster whitening speed, less tooth sensitivity, and/or less irritation. of oral soft tissue. The prior art has generally attempted to achieve improved bleaching efficiency or increased bleaching speed by increasing the content of the bleaching agent in the compositions. However, this approach has several problems. First, the participant may experience greater irritation and/or sensitivity, which may be associated with using a greater amount of whitening agent. In addition, some regulatory authorities and legislation in various regions around the world do not allow bleaching agents to be used in products at levels above certain concentrations. Therefore, despite the above known approaches to treating oral health issues, especially for teeth whitening, there is still a need to provide products with improved whitening efficacy, faster whitening speed, less tooth sensitivity, and/or less tooth irritation. oral soft tissues. The present invention overcomes some of the limitations of the prior art, and relates to a multi-phase mouthwash composition comprising a whitening agent, an aqueous phase and a hydrophobic phase, wherein, in certain embodiments, the hydrophobic phase may be in proportion predominant in relation to the aqueous phase.

SUMMARY OF THE INVENTION

[0004]Without being bound by theory, it has surprisingly been found that bleaching agents are effective at very low concentration if presented in a multi-phase oral composition as disclosed herein.

[0005] A tooth whitening kit is disclosed which comprises a multi-phase oral composition comprising, in certain embodiments, from about 0.002% to about 5%, by weight, of the multi-phase, one-phase, oral composition. aqueous which has a whitening agent; a hydrophobic phase; and a source of electromagnetic radiation capable of directing electromagnetic radiation of one or more wavelengths in the range from about 200 nm to about 1700 nm towards at least one tooth; wherein the multi-phase buccal composition may be a water-in-oil emulsion; wherein the concentration of the whitening agent may be up to about 0.1% by weight of the multi-phase buccal composition; and wherein, in certain embodiments, the hydrophobic phase may be a predominant portion of the multiphase buccal composition.

[0006] The present invention can be used to provide whitening benefits to the oral cavity by directly applying the composition to the teeth. In addition, the composition may be applied via an application support, such as a tape or film of material, a dental tray, a sponge material, or mixtures thereof. The application support may be attached to the teeth by the compositions of the present invention or the adhesion function may be provided independently of the compositions of the present invention (e.g. it may be provided by a separate adhesive composition used with the present compositions and an application support).

[0007]The application support can be fixed to the teeth by means of fixing that are part of the application support, for example, the application support can optionally be of sufficient size so that, once applied, it overlaps the soft tissues of the oral cavity making more of the surface of the teeth available for whitening. The delivery support can also be attached to the oral cavity through physical interference or mechanical interlocking between the delivery support and oral surfaces, including teeth.

[0008]The application support can be transparent or translucent to electromagnetic radiation with wavelengths from about 400 nm to about 500 nm. In certain embodiments, the application support enables about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%, 80%, 90%, or 100% of the electromagnetic radiation of about from 400 nm to about 500 nm passes through it.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 is a perspective view of a delivery system 10 comprising a tape of material 12 having rounded corners, on which in a second layer 14 the present compositions are applied as a coating.

[0010]Figure 2 is a cross-sectional view taken along section line 3-3 of Figure 1, showing an example of the tape.

[0011] Figure 3 is a cross-sectional plan view, showing the release system 10 attached to the teeth 22 by means of the composition of the second layer 14 located between the teeth 22 and the material tape 12.

[0012]Figure 4 is an elevational cross-sectional view of a tooth taken along section line 6-6 of Figure 3, showing the release system 10 adhesively attached to the teeth 22.

[0013] Figure 5 shows a dental tray 30 suitable for use with the composition of the present invention.

[0014] Figure 6 shows a device for applying electromagnetic radiation with a peak intensity wavelength of about 455 nm to a transparent mouthpiece to help reproducibly position the electromagnetic radiation towards the tooth surface; in accordance with certain embodiments of the present invention.

[0015]Figure 7 shows the whitening effectiveness on a natural tooth surface after 14 treatments using a composition of the present invention (Example IA applied to a tape and used with electromagnetic radiation with a peak intensity wavelength of 455 nm) .

[0016] Figure 8 illustrates water phase droplets versus air bubbles versus ink patterns as part of the procedure for measuring the two-dimensional density of water phase droplets of a multiphase buccal composition.

[0017]Figure 9 illustrates the procedure for applying the composition on peroxide test strips.

[0018]Figure 10 illustrates a digital image of the sample.

[0019]Figure 11 illustrates a digital image of the sample.

[0020]Figure 12 illustrates the container and roller mixer.

[0021]Figure 13 illustrates a digital image of the sample.

DETAILED DESCRIPTION OF THE INVENTION

[0022] The present invention comprises a multi-phase tooth whitening oral composition having an aqueous phase, which in certain embodiments can be in the range of from about 0.002% to about 5%, by weight, of the multi-phase oral composition. phases; a hydrophobic phase; and at least one active agent for oral care in the aqueous phase; wherein the active agent is a whitening agent which, in certain embodiments, may be present up to 0.1% by weight of the multiphase buccal composition.

[0023]By "composition for oral care", as used herein, is meant a product which, in its normal use, is not intentionally swallowed for the purpose of systemic administration of specific therapeutic agents, but is retained in the oral cavity for a sufficient time so that it comes into contact with dental surfaces and/or oral tissues. Examples of oral care compositions include dentifrice, tooth gel, subgingival gel, mouthwash, mousse, foam, mouthwash, lozenge, chewable tablet, tooth whitening strips, dental floss and dental floss coatings, soluble breath freshener strips or products adhesives and for denture care. The oral care composition may also be incorporated over tapes or films for direct application or attachment to oral surfaces.

[0024]The term "dentifrice" as used herein includes tooth or subgingival formulations in paste, gel or liquid form, unless otherwise specified. The dentifrice composition may be a single phase composition, or it may be a combination of two or more separate dentifrice compositions. The dentifrice composition can be in any desired form, such as deep streaked, surface streaked, multi-layered, with a gel surrounding the paste, or any combination thereof. Each dentifrice composition in a dentifrice comprising two or more separate dentifrice compositions may be contained in a physically separate compartment of a dispenser and be dispensed side by side.

[0025]The term "immiscible", as used herein, means that less than 1 part by weight of the substance dissolves in 99 parts by weight of a second substance.

[0026] The term "phase", as used herein, means a physically distinct region or regions, which may be continuous or discontinuous, having one or more properties that are different from another phase. Some non-limiting examples of properties that may differ between phases include composition, viscosity, solubility, hydrophobic ability, hydrophilic ability, and miscibility.

[0027] The term "multi-phase buccal composition", as used herein, comprises a mixture of two or more phases that are immiscible with each other, for example, water-in-oil emulsions. The phases can be continuous, discontinuous, or combinations thereof. Examples of multi-phase oral compositions include emulsions, such as water-in-oil emulsions. Examples of multi-phase oral compositions also include oil-in-water emulsions, water-in-oil-in-water emulsions and oil-in-water-in-oil emulsions. Examples of multiphase oral compositions also include compositions where the phases are multicontinuous, including bicontinuous, layered, striped, marbled, ribboned, swirled, and combinations thereof.

[0028] The term "multi-phase buccal composition", as used herein, comprises a mixture of two or more phases that are immiscible with each other, which form a water-in-oil emulsion. The phases can be continuous, discontinuous, or combinations thereof.

[0029] The term "emulsion", as understood in the present invention, is an example of a multi-phase buccal composition wherein 1) at least one of the phases is discontinuous and 2) at least one of the phases is continuous. Examples of emulsions include water droplets dispersed in oil. In this example, water and oil would be mutually immiscible with each other, water would be the discontinuous phase, and oil would be the continuous phase.

[0030] The term "water-in-oil emulsion", as understood in the present invention, is an example of an emulsion in which 1) the discontinuous phase is aqueous and 2) the continuous phase is hydrophobic.

[0031] The term "aqueous phase", as understood in the present invention, is at least one phase which comprises water and a bleaching agent, and is immiscible with the hydrophobic phase. In certain embodiments, each part of the aqueous phase contains at least 2% by weight of the aqueous phase bleaching agent. Optionally, the aqueous phase may further comprise ingredients that are water-soluble, water-miscible, or combinations thereof, such as, for example, water-soluble solvents, alcohol, poly(ethylene glycol), carbopol, etc. or mixtures thereof. In some embodiments, if and when immiscible fillers are added to the aqueous phase, the percentage of the aqueous phase in the composition is calculated by excluding the immiscible filler.

[0032] The term "hydrophobic phase", as understood in the present invention, means all components of the composition that are immiscible with the aqueous phase. Optionally, the hydrophobic phase may further comprise ingredients that are soluble, miscible, or combinations thereof, in the hydrophobic phase, such as, for example, hydrocarbon solvents dissolved in the hydrophobic phase, polyethylene dissolved in the hydrophobic phase, microcrystalline wax dissolved in the hydrophobic phase, or mixtures of the same.

[0033] The term "application support", as used herein, comprises a material or an apparatus that is used to secure the multi-phase buccal composition against the dental surface. Examples of application supports include dental tapes or trays.

[0034]The term "tape", as used herein, comprises a material 1) whose length of the longest dimension is generally greater than its width, and 2) whose width is generally greater than its thickness. Tapes can be rectangular, arched, curved, semi-circular, have rounded corners, have slits, have notches, be folded into three-dimensional shapes, or combinations thereof. Tapes can be solid, semi-solid, textured, moldable, flexible, deformable, permanently deformable, or combinations thereof. Tapes can be produced from plastic sheets including polyethylene or wax sheets. Examples of tapes include a piece of polyethylene about 66 mm long, 15 mm wide and 0.0178 mm thick. Examples of permanently deformable tapes include a piece of melt molding wax sheet about 66 mm long, 15 mm wide and 0.4 mm thick.

[0035]Multi-phase oral compositions, which in certain embodiments may be water-in-oil emulsions, are useful for topical application, in particular, for topical application in the mouth. For example, the composition may be an oral care composition; by "composition for oral care" or "multi-phase oral composition", as used herein, is meant a product which, in its normal course of use, is not intentionally swallowed for purposes of systemic administration of therapeutic agents, but is retained in the oral cavity for a time sufficient for it to come into contact with tooth surfaces for the purpose of whitening effectiveness.

[0036]As used herein, the word "or", when used as a connector of two or more elements, is intended to include the elements individually and in combination; for example, X or Y, means X or Y or both.

[0037] As used herein, the articles "a" and "an" are understood to mean one or more of the materials that are claimed or described, for example, "an oral care composition" or "a whitening agent".

[0038]As used herein, "safe and effective amount" means an amount of a component high enough to significantly (positively) modify the condition being treated or to produce the desired bleaching results, but low enough to avoid serious side effects ( a reasonable risk/benefit ratio), within the scope of sound medical/dental judgment. The safe and effective amount of a component will vary depending on the specific condition being treated, the age and physical condition of the patient being treated, the severity of the condition, the duration of treatment, the nature of the concurrent therapy, the specific form used and the vehicle. specific from which the component is applied.

[0039]As used herein, "a period of time sufficient to achieve bleaching" means that the composition is used by the participant or the participant is instructed to use the composition for longer than about 10 seconds; or more than about 1 minute, for example from about 2.5 minutes to about 12 hours (e.g. overnight treatment), or from about 3 minutes to about 180 minutes; or more than about 5 minutes, for example from about 5 minutes to about 60 minutes; or more than about 10 minutes, for example from about 10 minutes to about 60 minutes; or from about 1, 5, 10 or 15 minutes to about 20, 30, 60, 120 minutes per application; or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. Also, treatments can be applied from about 1, 2 or 3 times a day to about 4, 5, 6 or 7 times a day. Treatments can be applied for about 1, 2, 3, 4, 5, 6, or about 7 days to about 8, 9, 10, 11, 12, 13, 14, 21, 28 days or any other range. which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. Additionally, the extent of treatment to achieve the desired benefit, e.g. teeth whitening, may last for a specific period of time, which may be repeated if necessary, e.g. from about one day to about six months, in particular, from about one day to about 28 days, or from about 7 to about 28 days. The optimal duration and frequency of application will depend on the desired effect, the severity of any condition being treated, the health and age of the user, and similar considerations.

[0040] The term "dispenser" as used herein means any pump, tube or container suitable for dispensing oral care compositions.

[0041]As used here, "μm" or "micron", means micrometer.

[0042]The term "equivalent diameter" of a droplet, as used herein, means the diameter of a sphere that has the same volume as the droplet.

[0043]The term "two-dimensional droplet density", as used herein, means the number of droplets of the aqueous phase a) that are present in one square centimeter of a two-dimensional plane in the multiphase buccal composition and b) where the area in droplet cross section in the two-dimensional plane is greater than a specified value.

[0044]All percentages and ratios used in this document are expressed in weight of the total composition (%, by weight), unless otherwise indicated. All percentages, ratios and contents of ingredients mentioned herein are based on the actual amount of the ingredient and do not comprise solvents, fillers or other materials with which the ingredient may be combined in the form of a commercially available product, unless otherwise indicated. For example, a composition that contains 0.2857% of a 35% aqueous solution of hydrogen peroxide H2O2 and 99.7143% of petrolatum would mean that this composition contains 0.2857% of an aqueous phase (the aqueous solution of H2O2 at 35%) and 99.7143% of a hydrophobic phase (the petrolatum) and 0.099995% of a whitening agent (the H2O2 in the aqueous phase). As another example, a composition that contains 0.2857% of a 35% aqueous H2O2 solution, 89.7143% of petrolatum, and 10% of silica dispersed in petrolatum would mean that such a composition contains 0.2857% of an aqueous phase. (the 35% aqueous H2O2 solution), 99.7143% of a hydrophobic phase (the petrolatum and the silica which are both immiscible with the aqueous phase) including the 10% of a filler (the silica) and 0.099995% of a whitening agent (the H2O2 in the aqueous phase). This also means that this composition has a ratio of the weight percent concentration of whitening agent present in the aqueous phase to the weight percent concentration of whitening agent present in the total multi-phase oral composition of 350.02 (i.e. that is, 35% divided by 0.099995%).

[0045] As yet another example, a multi-phase buccal composition that contains 0.2857% of a 35% aqueous hydrogen peroxide (H2O2) solution, 99.6143% of petrolatum, and 0.1% of Cross-linked siloxane dispersed in the aqueous phase would mean that this multi-phase buccal composition contains 0.2857% of an aqueous phase (i.e., the 35% aqueous H2O2 solution), 99.7143% of a hydrophobic phase (i.e., the petrolatum and the cross-linked siloxane particles which are both immiscible with the aqueous phase), 0.099995% of a whitening agent (i.e. the H2O2 in the aqueous phase) and 0.1% of a filler (i.e. the particles of cross-linked siloxane). This means that this composition has a ratio of the weight percent concentration of bleaching agent present in the aqueous phase to the weight percent concentration of bleaching agent present in the total multi-phase oral composition of 350.02 (i.e. , 35% divided by 0.099995%).

[0046]All measurements mentioned herein are made at 23°C (ie ambient temperature), unless otherwise noted.

[0047]The "active ingredients and other ingredients" useful in the present invention may be categorized or described in this invention by their cosmetic and/or therapeutic benefit, or by their postulated modes of action or function. However, it should be understood that the active ingredient and other ingredients useful to the present invention may, in some cases, provide more than one function or more than one cosmetic and/or therapeutic benefit, or may operate through more than one mode of delivery. action. Therefore, the classifications provided herein are for convenience and are not intended to limit an ingredient to a particularly defined function(s) or activities mentioned.

[0048]As used herein, the term "teeth" refers to natural teeth as well as artificial teeth or dentures, and is interpreted to encompass one tooth or multiple teeth. The term "dental surface" as used herein refers to the surface(s) of natural teeth as well as the surface(s) of artificial teeth or surface(s) of dentures, accordingly.

[0049] The term "buccally acceptable carrier" comprises one or more compatible solid or liquid excipients or diluents which are suitable for topical buccal administration. As used herein, "compatible" means that the components of the composition are suitable for mixing together without any interaction occurring that would substantially reduce the stability and/or effectiveness of the composition. Multi-phase oral compositions

[0050] The multi-phase oral compositions as disclosed herein, in certain embodiments, may be water-in-oil emulsions. The multi-phase oral compositions can be microemulsions or macroemulsions.

[0051]For water-in-oil emulsions comprising a whitening agent, it has surprisingly been found that the droplet size of the aqueous phase is a factor in decreasing oral/topical irritation and/or tooth sensitivity. Without being bound by theory, if the droplet size of the aqueous phase is too large, this can lead to large stains on oral/topical/dental surfaces that are exposed to a high concentration of the whitening agent which, in turn, can lead to oral/topical irritation and/or tooth sensitivity. In certain embodiments, the numerical equivalent average diameter or the volumetric average equivalent diameter of the droplets of the aqueous phase may not be greater than about 0.001 micrometer, 0.01 micrometer, 0.1 micrometer, 1 micrometer, 5 micrometers, 10 micrometers, 50 micrometers, 100 micrometers, 500 micrometers, or 1000 micrometers or any other narrower numerical range and which is contained in such numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the numerical equivalent average diameter or the volumetric average equivalent diameter of the aqueous phase droplets can be from about 0.001 micrometer to about 1000 micrometers, preferably from about 0.01 micrometer to about 1000 micrometers, with more preferably from about 0.1 micrometer to about 100 micrometers, and most preferably from about 1 to about 100 micrometers or any other narrower numerical range and which is contained in such a narrower numerical range as if such narrower numerical ranges were expressly written in the present invention. Compositions that have a high density of large droplets in the aqueous phase can lead to oral/topical irritation and/or tooth sensitivity. It is worth noting that measuring the numerical equivalent mean diameter or the volumetric mean equivalent diameter of the aqueous phase droplets requires a procedure to measure the entire droplet size distribution in three dimensions - this may require multiple different techniques that are suitable for small droplets, medium and large. In contrast, the procedure specified here for measuring "two-dimensional droplet density" can be used to measure only large droplets and only in two dimensions - this can be done using an optical microscope by counting the number of larger droplets. than a specified size (in the two-dimensional focal plane), and does not require more complex equipment. In certain embodiments, the "two-dimensional droplet density" of the aqueous phase measured using the procedure specified herein, with a cross-sectional area greater than about 1000, 3000, 10000, 20000, or 50000 square micrometers may be no more than about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100 per square centimeter of the two-dimensional plane, or any other numerical range that is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the "two-dimensional droplet density" of the aqueous phase measured using the procedure specified herein, with a cross-sectional area greater than about 10,000 square micrometers may be no more than 25, preferably no more than 10, most preferably not more than 5 and most preferably not more than 1 per square centimeter of the two-dimensional plane or any other narrower numerical range and which is contained in such a wider numerical range as if such narrower numerical ranges were expressly written in the present invention. Procedure for measuring two-dimensional droplet density of the aqueous phase of a multiphase buccal composition 1. Cut a 20 x 20 mm grid from an adhesive grid label* (available from Diversified Biotech Dedham, MA, USA item number GRID -1000; purchased from VWR, Batavia, IL, USA, catalog number 89032-163) and attach it to the top of a glass microscope slide (VWR Micro Slides, Super Frost Plus, 25 x 75 x 1 mm, produced by VWR International, Radnor, PA, USA; purchased from VWR, Batavia, IL, USA, catalog number 48311-703). * each grid sticker has two 20 x 20 mm grids side by side, and each cell inside each grid measures 1 x 1 mm. 2. Use a small spatula and place a small sample of the composition in the middle of the adhesive grid label attached to the microscope slide. The amount of sample should be such that after being pressed down according to step 3, at least 100 grid cells are completely covered with the composition and can be measured. Take care to place the sample as a single drop on the adhesive grid label - this helps to minimize air trapping when the coverslip is placed over it. 3. Place a coverslip (VWR Microscope Cover Glasses, 22 x 22 mm, purchased from VWR, Batavia, IL, USA, catalog number 16004-094) over the sample composition and press until the sample composition is approx. 100 micrometers thick. This can be done by placing a second microscope slide over the coverslip and inserting a pair of coverslips as spacers on each side of the sample composition between the two microscope slides and manually pressing until the sample is about 100 micrometers thick. . Note that to ensure that each individual sample is approximately 100 micrometers thick, the thickness of each individual grid adhesive label, coverslip, and microscope slide will need to be measured. 4. Note that to ensure that each individual sample is approximately 100 micrometers thick, the thickness of each individual grid adhesive label, coverslip, and microscope slide will need to be measured. Use a microscope and a level of magnification that a) provides a field of view that covers at least an entire cell of the grid, so that all four edges of the cell are visible within the field of view, and b) allows for area measurement in cross-section of aqueous phase droplets greater than the specified value. 5. Center the field of view on a single grid cell. Count the number of droplets of the aqueous phase that: a) are visible in the cell (including those on the grid lines, but taking care not to count the same twice); and b) whose cross-sectional area in the two-dimensional focal plane is greater than the specified value. Be careful not to count residual air bubbles (unlike water phase droplets, air bubbles can be identified by thick dark walls in the field of view), or ink pattern features on the adhesive grid label (unlike droplets from aqueous phase, the ink pattern features are agglomerated and appear only on the grid lines). Figure 8 shows a sample image of water phase droplets versus air bubbles versus ink pattern characteristics. 6. Repeat step 5 for each cell that is completely covered by the composition. There must be at least 100 cells completely covered by the composition per slide. 7. The "two-dimensional droplet density" with a cross-sectional area greater than a specified value (expressed as the number of droplets per square centimeter) for this slide is calculated as: the total number of droplets of the aqueous phase whose sectional area cross-sectional area in the two-dimensional focal plane is greater than the value specified in all cells measured on this slide DIVIDED by the total area of all cells measured on this slide expressed in square centimeters. 8. Repeat steps 1 through 7 for a total of at least twelve slides. Average in step 7 for all measured slides. This is the final "two-dimensional droplet density" with a cross-sectional area greater than a specified value (expressed as number of droplets per square centimeter).

[0052]For multi-phase oral compositions comprising peroxide, it has surprisingly been found that the standard deviation of the peroxide concentration of a multi-phase oral composition spread over the peroxide test strips is a factor in decreasing oral irritation. /topical and/or tooth sensitivity during use. Each peroxide test strip has two reaction zones that change color (leading to a lower intensity of RED) in areas or points that are brought into contact with peroxide. Thus, without being bound by theory, peroxide test strips can be conveniently used as a substitute for oral/topical/dental surfaces to identify high peroxide stains that can lead to oral/topical irritation and/or tooth sensitivity. In addition, since contact with peroxide leads to lower RED intensity in the reaction zones, the average RED intensity of the peroxide test strips rubbed with the multi-phase buccal composition subtracted from the reference average RED intensity. of the untreated peroxide test strips can conveniently be used as a measure of the average peroxide concentration. Multi-phase buccal compositions that have large points of high peroxide concentration when the multi-phase buccal composition is applied to the peroxide test strips may also have large points of high peroxide concentration when the multi-phase buccal composition is applied. to oral/topical/dental surfaces - this in turn can lead to oral/topical irritation and/or tooth sensitivity. In contrast, multi-phase buccal compositions that have only small dots of high peroxide concentration when the multi-phase buccal composition is applied over the peroxide test strips may also have only small dots of high peroxide concentration when the multi-phase oral composition is applied to oral/topical/dental surfaces - this in turn can lead to low oral/topical irritation and/or tooth sensitivity. Peroxide concentration points when the multi-phase buccal composition is applied to peroxide test strips can be quantified by the standard deviation of the peroxide concentration on the test strips measured using the procedure specified herein. Multi-phase buccal compositions that have large points of high peroxide concentration when the multi-phase buccal composition is applied onto peroxide test strips have a high standard deviation of the peroxide concentration on the test strips. In contrast, multi-phase buccal compositions that have only small points of high peroxide concentration when the multi-phase buccal composition is applied onto peroxide test strips have a low standard deviation of the peroxide concentration on the test strips.

[0053] In addition, multi-phase mouthwash compositions with large droplets can cause large points of high peroxide concentration when the multi-phase buccal composition is applied over peroxide test strips - this, in turn, can lead to a high standard deviation of the peroxide concentration on the test strips. In contrast, multi-phase buccal compositions that have few large droplets or that do not have large droplets can cause only small spots of high peroxide concentration when the multi-phase buccal composition is applied over peroxide test strips - this in turn turn can lead to a low standard deviation of the peroxide concentration on the test strips.

[0054]In certain embodiments, the standard deviation of the peroxide concentration of a multi-phase buccal composition applied to the peroxide test strips measured using the procedure specified herein may be no greater than about 5, 10, 15 , 20, 25, 30, 40, 50 or 100 or any other numerical range, which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments the standard deviation of the concentration of peroxide of multi-phase buccal composition applied to the peroxide test strips measured using the procedure specified herein may be no more than about 50, preferably no more than about 25, with most preferably not more than about 10, and most preferably not more than about 5, or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0055]For multi-phase oral compositions comprising peroxide, it has surprisingly been found that the average peroxide concentration of a multi-phase oral composition applied over peroxide test strips is a factor in providing bleaching efficacy. Without being bound by theory, if the average concentration of peroxide of a multi-phase oral composition applied to the peroxide test strips is low, the average concentration of peroxide applied to the surface of the teeth during use may also be low, which could lead to low whitening effectiveness. On the contrary, if the average peroxide concentration of a multi-phase oral composition applied to the peroxide test strips is high, the average concentration of peroxide applied to the surface of the teeth during use may also be high, which could lead to a High whitening effectiveness. In certain embodiments, the average peroxide concentration of a multi-phase buccal composition applied to peroxide test strips measured using the procedure specified herein may be about 1, 2, 5, 10, 15, 20, 25. 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or 225 at about 2, 5, 10, 15 , 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or 225 or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the average peroxide concentration of a multi-phase buccal composition applied to peroxide test strips measured using the procedure specified herein can be from about 1 to about 100, more preferably from about 2 to about 75, more preferably from about 5 to about 50, and most preferably from about 10 to about 50 or any other numerical range which is narrower and which is contained within such a wider numerical range , as if such narrower numerical ranges were expressly written in the present invention.

[0056]For multi-phase buccal compositions comprising peroxide, it was surprisingly found that the ratio of the average peroxide concentration of a multi-phase buccal composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of a multi-phase oral composition applied to the peroxide test strips is a factor in providing a high ratio of bleaching efficacy to oral/topical irritation and/or tooth sensitivity. Without being bound by theory, if the ratio of the average peroxide concentration of a multi-phase buccal composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of a multi-phase buccal composition applied to the peroxide test strips peroxide is high, the composition can provide high efficacy combined with low oral/topical irritation and/or tooth sensitivity during use. In contrast, if the ratio of the average peroxide concentration of a multi-phase buccal composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of a multi-phase buccal composition applied to the peroxide test strips is low , the composition may provide low efficacy combined with high oral/topical irritation and/or tooth sensitivity during use. In certain embodiments, the ratio of the average peroxide concentration of a multi-phase buccal composition applied to peroxide test strips measured using the procedure specified herein and the standard deviation of the peroxide concentration of a multi-phase buccal composition applied on peroxide test strips measured using the procedure specified herein, may be at least about 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4,5, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50 or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the ratio of the average peroxide concentration of a multi-phase buccal composition applied to peroxide test strips measured using the procedure specified herein and the standard deviation of the peroxide concentration of a multi-phase buccal composition applied on peroxide test strips measured using the procedure specified herein may be at least about 0.5, preferably at least about 1, more preferably at least about 2, and most preferably at least about 3.5, or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. Method for Measuring the Mean and Standard Deviation of the Peroxide Concentration of a Multiphase Buccal Composition Applied to Peroxide Test Strips 1. Weigh 0.60 to 0.80 grams of the composition onto the end of a clean hard rubber spatula ( 10 cm (4") long blade, obtained from VWR, Batavia, IL 60510, USA, catalog number 57930-025. 2. Take a new peroxide test strip (EMD Millipore Corporation, Billerica, MA, from supplier 1.16974.0001; purchased from VWR, Batavia, IL, USA, catalog number EM1.16974.0001) of the container, and start a timer. 3. Obtain a digital image of the peroxide test strip. Equipment and The systems used to take the digital image of the test strip are specified in the present invention. The digital images of the sample are shown as Figures 10 and 11. Place the peroxide test strip on a clean paper towel. 4. Hold the spatula and the peroxide test strip as shown in Fig. ra 9. Apply the composition (pre-weighed in step 1) with firm pressure from left to right over both reaction zones on the test strip. Repeat the application movement a total of three times from left to right with the same sample of composition that has already been pre-weighed on the spatula. 5. Move the peroxide test strip to a clean area of the paper towel. Place a filter paper (Whatman standard grade qualitative filter paper grade 1, circle, 90 mm, supplier number 1001-090; purchased from VWR, Batavia, IL, 60510, USA, catalog number 28450-081) over the test. Apply pressure with your fingers on the filter paper. Pull the peroxide test strip from below the filter paper (while maintaining finger pressure on the filter paper) in a single stroke so that excess gel is removed by the filter paper and paper towel. Make sure the reaction zones do not dislodge from the peroxide test strip. 6. Take a digital image of the peroxide test strip. The configuration of the equipment and system used to digitally image the test strip are specified in the present invention. The digital images of the sample are shown as Figures 10 and 11. 7. Steps 2 through 6 must be completed within the 90 seconds indicated on the timer. 8. Repeat steps 1 through 7 for a total of at least eighteen peroxide test strips. 9. Use Adobe Photoshop CS4 with the procedure specified here to measure the mean and standard deviation of the RED intensities of the Munsell N8 matte color sheet tape attached to the backing that serves as an internal reference for Munsell N8 within each image. The average RED intensity of the Munsell N8 internal reference within each image must be 204 to 212 and the standard deviation must not be greater than 3. 10. Use Adobe Photoshop CS4 with the procedure specified here to measure the mean and standard deviation of the RED intensities of each reaction zone on all peroxide test strips in the BASELINE (prior to applying the composition). 11. Use Adobe Photoshop CS4 with the procedure specified here to measure the mean and standard deviation of the RED intensities of each reaction zone on all peroxide test strips AFTER compounding. 12. The average peroxide concentration of the composition applied to the peroxide test strips is calculated as follows: First, calculate the average baseline RED intensity of each step 10 reaction zone MINUS the average RED intensity of the same reaction zone after applying the composition from step 11. Repeat this calculation for all reaction zones, and average the results across all reaction zones on all peroxide test strips. This is the average peroxide concentration of the composition applied to the peroxide test strips. 13. The standard deviation of the peroxide concentration of the composition applied to the peroxide test strips is calculated as follows: Average the standard deviation of the RED intensities in all reaction zones on all peroxide test strips AFTER they have been applied with the composition from step 11. This is the standard deviation of the peroxide concentration of the composition applied to the peroxide test strips.

[0057]To validate the equipment, system configuration and procedure specified here, the mean and standard deviation of the red intensities of a Munsell N8 matte color sheet (from Munsell Color, Division of Xrite, Grand Rapids, MI, USA) need to be measured and have been shown to be 204 to 212 for the mean and a maximum of 3 for the standard deviation. Equipment for taking digital images from peroxide test strips 14. - Digital camera capable of capturing images in jpg format at a resolution of 18 million pixels (5184x3456) and capable of reaching a shutter speed of 1/250° of one second (such as Canon 60D camera from Canon USA Inc., Lake Success, NY 11042, USA) 15. - Memory card 1 - Lens adapter, if needed (such as Nikon lens to Canon body adapter) 1 - Lens 105mm (as a 105mm Micro Nikkor lens available from Nikon USA Inc. Melville, NY 11747, USA) 1 - 52mm flash adapter ring 1 - Macro lite ring with fixed polarization filter (as Macro ring lite Canon MR-14EX with Fixed Polarization Filter available from Canon USA Inc., Lake Success, NY 11042, USA) 1 - 52mm Swivel Circular Polarizer on Lens 1 - Tripod 1 - Munsell N8 Matte Color Sheet (available together Munsell Color, X-rite Division, Grand Rapids, MI, USA) 1 - Support for test strips and peroxides produced using DGK's XL gray plastic card (available from DGK Color Tools at Amazon.com) as the background, and a Munsell N8 matte color foil tape attached to serve as an internal Munsell N8 reference inside each Image. 1- Millimeter scale mounted on blank specimen tape System setup for taking digital images of peroxide test strips 1. The tripod is set up with the tripod bracket attached to the underside of the tripod to accommodate macro photography, with the camera pointing down towards the table. The exposure plane is 317 mm from the sensor plane. 2. The 105mm Nikorr lens is attached to the Canon 60D camera body using the Canon to Nikon adapter bracket. 3. The swivel polarizer is attached to the 105mm Micro Nikkor lens. 4. The 52mm flash adapter ring is attached to the front of the 105mm lens. 5. Canon's Macro lite MR-14EX ring with polarizing filter is attached to the front of the lens on the flash adapter ring. 6. The rotating circular polarizer on the lens is rotated until maximum glare/reflection is removed and full cross polarization is achieved. 7. The flash is set to "manual" mode with the power setting set to 1/8 power. 8. The Canon 60D camera is set to "manual" mode with the ISO setting to 100. 9. The shutter is set to 1/250th of a second. 10. Aperture is set to f=8 on the 105mm Micro Nikkor lens. 11. Manual focus is used over the 105mm Micro Nikkor lens with focus for a distance of 317mm from the sensor plane to the exposure plane. 12. A mounted sheet of calibrated Munsell N8 material is used to achieve white balance for the images. 13. The camera is set to capture images in a jgp image with a resolution of 18 million pixels (5184x3456). 14. The total exposure setting for the camera and flash needs to be configured so that an image captured from the Munsell N8 matte color sheet has an average RED intensity of 204 to 212 and a standard deviation of at most 3 measured with use of the procedure specified here. Procedure in Adobe Photoshop CS4 to measure the mean and standard deviation of RED intensities 1. Open Adobe Photoshop CS4. 2. At the top edge of the screen, select "Window", followed by "Histogram". This shows the histogram of the image. In the Histogram window, select "Expanded view" and "Show statistics". This shows the histogram with the statistics. Make sure the "Channel" is set to "RED" (red). In Adobe Photoshop CS4, a histogram panel shows the tonal range of an image. It shows how pixels are distributed by plotting the number of pixels at each of 256 intensity levels from 0 to 255 in the selected region of interest. Pixels with the same intensity level are stacked in bars along the vertical axis. The larger the bar, the greater the number of pixels at that intensity level. Vertical bars towards the right side of the histogram indicate pixels with higher intensities, while bars towards the left side of the histogram indicate pixels with lower intensities. 3. The mean and standard deviation of the RED intensities of the Munsell N8 matte color sheet is measured as follows: Open a captured image of the Munsell N8 matte color sheet using Adobe CS4. On the left edge of the screen, select the "Rectangular Marquee Tool". At the top edge of the canvas, set "Feather" to 0 px, "Style" to fixed size, "Width" to 5000 px and "Height" to 3300 px. This defines a rectangle containing the 16,500,000 pixels whose size and shape matches the size and shape of the Munsell N8 matte color sheet images. Select the Munsell N8 matte color sheet image using the "Rectangular Marquee Tool". Make sure the edges of the rectangle are within the edges of the Munsell N8 matte color sheet image. Click on the circular symbol in the Histogram panel and make sure the "Cache Level" reads 1 in the Histogram panel. This measures and displays the mean and standard deviation of the RED intensities of the Munsell N8 matte color sheet. Record these values. 4. The mean and standard deviation of the Munsell N8 internal reference RED intensities within each image are measured as follows: Open a captured image of the Munsell N8 internal reference within each reference image using Adobe CS4. On the left edge of the screen, select the "Rectangular Marquee Tool". At the top edge of the canvas, set "Feather" to 0 px, "Style" to fixed size, "Width" to 5,000 px, and "Height" to 800 px. This defines a rectangle containing 4,000,000 pixels, whose size and shape correspond to the size and shape of the Munsell N8 internal reference within each image. Select the Munsell N8 internal reference within each image using the "Rectangular Marquee Tool". Make sure the edges of the rectangle are within the edges of the Munsell N8 internal reference within each image. Click on the circular symbol in the Histogram panel and make sure the "Cache Level" reads 1 in the Histogram panel. This measures and displays the mean and standard deviation of the Munsell N8 internal reference RED intensities within each image. Record these values. 5. The mean and standard deviation of the RED intensities of each reaction zone on the peroxide test strip are measured as follows: Open a captured image of the peroxide test strip using Adobe CS4. On the left edge of the screen, select the "Rectangular Marquee Tool". At the top edge of the canvas, set "Feather" to 0 px, "Style" to fixed size, "Width" to 1300 px, and "Height" to 1750 px. This defines a rectangle containing 2,275,000 pixels whose size and shape correspond to the size and shape of the images of each reaction zone on the peroxide test strip. Select one of the two reaction zones on the peroxide test strip using the "Rectangular Marquee Tool". Check that the edges of the rectangle are within the edges of the reaction zone. Click on the circular symbol in the Histogram panel and make sure the "Cache Level" reads 1 in the Histogram panel. This measures and displays the mean and mean deviation of the RED intensities of one of the two reaction zones on the peroxide test strip. Record these values.

[0058] The components of the aqueous phase and the hydrophobic phase are chosen to readily enable the release of the whitening agent situated in the aqueous phase from the composition.

[0059] Without being bound by theory, it is believed that when the present invention, which in certain embodiments may be in the form of a water-in-oil emulsion, is brought into contact with a dental surface, the aqueous phase and aqueous phase components can migrate to the tooth surface. The possible net effect is that the teeth whitening effect is initiated only after contact with the tooth surface to be treated. This means that the whitening agent can be covered, protected from environmental influences and thus stabilized by the hydrophobic phase of the multi-phase oral composition until use and potentially by the hydrophobic phase in the form of a film or layer during use. Thus, the effect of the active can be applied to the tooth surface and the active agent, for example, the whitening agent can be potentially shielded from the oral environment during use. Thus, the effectiveness of a multistage bleaching oral composition can be enhanced and/or accelerated.

[0060] Without being bound by theory, the present invention can improve the release of the whitening agent to the surface of teeth and thus the whitening performance, due to the partially hydrophobic and partially hydrophilic nature of the composition. Due to the resulting drive force, the whitening agent present in the aqueous phase can be directed to the tooth surface. Thus, increased bleaching speed and increased effectiveness of the bleaching agent can be achieved, although surprisingly low total levels of the bleaching agent are used. The present invention, therefore, at a given general total concentration, such as 0.1%, 1%, or 5% by weight, or less of a whitening agent, provides a surprisingly high degree of bleaching, may require fewer applications to achieve. achieve the same degree of whitening or may require a lower gel load (milligrams of gel per unit area) to obtain the same degree of whitening.

[0061] In addition, retention of the multi-phase buccal composition on dental surfaces can be enhanced as the hydrophobic phase resists salivary dilution and salivary enzymes that can decompose the peroxide. In addition, the hydrophobic phase does not dehydrate teeth by creating an outward flow of water as created by many hydrophilic compositions containing hydrophilic adhesives such as polycarboxylic acid. Since the hydrophobic phase does not dehydrate teeth, this can result in a surprisingly low level of tooth sensitivity while additionally providing a surprisingly high level of whitening effectiveness.

[0062] In addition, the hydrophobic phase can provide additional advantages. For example, the hydrophobic phase represents a stable matrix for ingredients that are soluble in the hydrophobic phase. For example, many flavoring ingredients generally used in multi-phase oral compositions are soluble in the hydrophobic phase. This means that the flavoring ingredients can be protected against any influence of the active agent, for example the whitening agent in the multi-phase mouthwash. Furthermore, during the use of the multi-phase oral composition on the tooth surface at least part of the hydrophobic phase may be situated - without being bound by theory - towards the soft oral tissues, such as the mucosa, thus presenting the ingredients that are present in the oral cavity. hydrophobic phase, such as flavoring compounds, to the oral cavity. Furthermore, the hydrophobic phase can protect the active agent, such as the whitening agent, against any influence from the oral cavity, such as dilution by saliva. The shielding effect can also apply to the dental (dental) surface(s) itself, with the hydrophobic phase providing greater hydration of the dental surfaces.

[0063] In certain embodiments, the multiphase oral compositions of the present invention may be in the form of a liquid, a viscous liquid, a gel, a semi-solid, a solid, a particulate, a powder, a viscoelastic liquid, a gel. viscoelastic, a colloidal solution, a viscoelastic solid, or any combination thereof. aqueous phase

[0064] The present multi-phase buccal composition comprises an aqueous phase. In certain embodiments, the maximum amount of aqueous phase may be 0.3%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40 %, 50% or 60%, by weight, of the multi-phase mouthwash composition or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention .

[0065] In certain embodiments, the amount of aqueous phase may be about 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, 0.01% or 0.002% by weight of the multi-phase buccal composition at about 60%, 55% , 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0, 3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0, 02%, 0.01% or 0.002%, by weight, of the multiphase oral composition or any other numerical range which is narrower and which is contained in such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the amount of aqueous phase can be from about 0.002% to about 5%, from about 0.1% to about 2%, from about 0.1% to about 1%, or from from about 0.1% to about 0.5% by weight of the multiphase buccal composition, or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such further numerical ranges narrow lines were expressly written in the present invention. In certain embodiments, the amount of aqueous phase may be less than about 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5% , 4%, 3%, 2%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1%, 0.9%, 0.8%, 0, 7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0, 06%, 0.05%, 0.04%, 0.03%, 0.02%, or 0.01%, by weight, of the multiphase oral composition or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the amount of aqueous phase may be less than about 1.0% or 0.9%, by weight, of the multiphase buccal composition. In certain embodiments, the aqueous phase can be from about 0.002% to about 5%, preferably from about 0.01% to about 5%, more preferably from about 0.1% to about 5% %, and most preferably from about 1% to about 5%, by weight, of the multi-phase buccal composition or any other numerical range which is narrower and which is contained within such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0066] In certain embodiments, the aqueous phase can be from about 0.002% to about 15%, preferably from about 1% to about 15%, more preferably from about 5% to about 15% , and most preferably from about 5% to about 10%, by weight, of the multi-phase buccal composition or any other numerical range which is narrower and which is contained within such wider numerical range, as if such ranges narrower numbers were expressly written in the present invention.

[0067] In certain embodiments, the aqueous phase can be from about 0.9% to about 60%, preferably from about 6% to about 30%, more preferably from about 7% to about 7% 20%, and most preferably from about 10% to about 30%, by weight, of the multiphase buccal composition or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0068] The aqueous phase may include water, polyalkylene glycols having molecular weights of from about 200 to about 20,000, humectants and mixtures thereof. Humectants generally include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, butylene glycol, poly(ethylene glycol) and propylene glycol, and mixtures thereof. In certain embodiments, the aqueous phase may comprise at least about 10%, or at least about 20%, by weight, of water in the aqueous phase.

whitening agent

[0069] The present multi-phase oral compositions further comprise a safe and effective amount of a whitening agent, the content of the whitening agent being based on the available oxygen or chlorine, respectively, which the molecule is capable of providing. to lighten the stain. In certain embodiments, the maximum amount of whitening agent may be 0.1%, 1%, 5%, 10%, 15%, or 20%, by weight, of the multi-phase oral composition or any other numerical range that is more narrow and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0070]In certain embodiments, the whitening agent may be present of about 0.001%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.095% 0.099995%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6 %, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15% or 20% to about 0.001%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0, 09%, 0.095% 0.099995%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15% or 20% by weight of the multi-phase oral composition or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0071]In certain embodiments, the content of whitening agent may be less than 0.09%, 0.095% 0.099995%, 0.1%, 0.2%, 0.3%, 0.4%, 0 .5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% , or 10% by weight of the multiphase buccal composition, in some embodiments less than 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4% , 0.3%, 0.2%, or 0.1% by weight of the multi-phase buccal composition, preferably from about 0.1% to about 0.9%, more preferably from from about 0.2% to about 0.8%, more preferably from about 0.3% to about 0.7%, by weight, of the multiphase buccal composition or any other numerical range which is more narrow and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the bleaching agent may be present from about 0.001% to about 1%, preferably from about 0.01% to about 0.1%, most preferably from about 0.1% to about 1%, and most preferably from about 0.5% to about 1%, by weight, of the multi-phase buccal composition or any other numerical range which is narrower and which is contained within such numerical range wider, as if such narrower numerical ranges were expressly written in the present invention.

[0072] In certain embodiments, the lightening agent may be present from about 0.6% to about 5%, preferably from about 0.6% to about 4%, most preferably from about 1 % to about 4%, and most preferably from about 1% to about 3%, by weight, of the multiphase buccal composition or any other numerical range which is narrower and which is contained within such a narrower numerical range. broad, as if such narrower numerical ranges were expressly written in the present invention.

[0073] In certain embodiments, the lightening agent may be present from about 0.6% to about 10%, preferably from about 0.6% to about 6%, most preferably from about 1 % to about 5%, and most preferably from about 1% to about 3%, by weight, of the multi-phase buccal composition or any other numerical range which is narrower and which is contained in such a narrower numerical range. broad, as if such narrower numerical ranges were expressly written in the present invention.

[0074]The bleaching agent content can be based on the available oxygen or chlorine, respectively, which the molecule is able to provide to lighten a stain. In certain embodiments, the whitening agent content is less than about 0.1% by weight of the multiphase oral composition, in certain embodiments less than about 0.09%, 0.08%, 0.07 %, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, 0.01%, or 0.001% by weight of the multi-phase buccal composition, or about 0 .01% to about 0.099995%, about 0.01% to about 0.095%, or about 0.05% to about 0.09%, by weight, of the multi-phase buccal composition, or any another numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. Surprisingly, the whitening agent is significantly effective when used even at low levels in the multi-phase oral compositions as disclosed herein.

[0075] In certain embodiments, the present multi-phase oral compositions comprise a whitening agent, wherein the whitening agent is present in the aqueous phase of about 2%, 5%, 8.75%, 10%, 15% , 17.5%, 20%, 25%, 30%, 35%, 45%, 50%, 60%, or 67% to about 67%, 60%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 17.5%, 15%, 10%, 8.75%, or 5%, by weight, of the aqueous phase or any other numerical range which is narrower and which is contained in such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0076]In certain embodiments, the bleaching agent in the aqueous phase may be present at least or more than 17.5%, 20%, 25%, 30%, 35%, 45%, 50%, or 60%, by weight of the aqueous phase or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. Ratio of whitening agent concentrations

[0077] In certain embodiments, the multi-phase mouthwash compositions of the present invention provide a high ratio of the percentage by weight concentration of bleaching agent present in the aqueous phase to the percentage by weight concentration of bleaching agent present in the total amount. multi-phase buccal composition, since they have a high concentration by weight percentage of whitening agent present in the aqueous phase combined with a relatively low concentration by weight percentage of whitening agent present in the total of the multi-phase oral composition. Without being bound by theory, this surprising combination of seemingly contradictory parameters in the present invention releases the whitening agent onto the surface of the teeth with a high driving force even when the total concentration or amount of whitening agent applied to the surface of the teeth is different. low. Consequently, 1) the high driving force provides a surprisingly high level of bleaching effectiveness and/or bleaching speed, while 2) the low overall concentration or low amount of bleaching agent applied to the tooth surface can help reduce tooth sensitivity. .

[0078] The ratio between the weight percent concentration of whitening agent present in the aqueous phase and the weight percent concentration of whitening agent present in the total multi-phase oral composition can be about 67000, 50000, 35000 I , 70, 60, 50, 40, 30, 20, 15, 10, or 5 to about 67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500, 2000, 1750, 1160, 1000, 875, 70 580, 500, 430, 400, 380, 350, 200, 175, 111, 110, 105, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 or any other range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0079] In certain embodiments, the present multi-phase oral compositions comprise a whitening agent, wherein the ratio of the percentage by weight concentration of whitening agent present in the aqueous phase to the percentage by weight concentration of the whitening agent present in the total multi-phase buccal composition can be at least or more than about 67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500, 2000, 1750, 1160, 1000, 875, 700, 580, 500, 430, 400, 380, 350, 200, 175, 110, 105, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 or any other numerical range that is narrower and that is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0080]Suitable whitening agents include agents that provide whitening effects, stain whitening effects, stain removal effects, stain color changing effects, or any other effect that changes or lightens the color of the tooth. For example, in certain embodiments, the bleaching agents comprise a source of peroxide radicals. In addition, bleaching agents may include peroxides, metal chlorites, perborates, percarbonates, peroxyacids, persulfates, compounds that form the aforementioned compounds in situ, and combinations thereof. Suitable peroxide compounds include hydrogen peroxide, urea peroxide, calcium peroxide, carbamide peroxide and mixtures thereof. In certain embodiments, the bleaching agent may be hydrogen peroxide (H2O2). Suitable metal chlorites include calcium chlorite, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite, potassium chlorite and mixtures thereof. Additional bleaching agents also include hypochlorite (such as metal hypochlorites) and chlorine dioxide. Persulfates include salts of peroxy monopersulfate, peroxy disulfate and mixtures thereof. The initial bleaching agent can be an aqueous or solid material.

[0081] The bleaching agents of the present invention can be stabilized against degradation through the shielding effect of the hydrophobic phase. In certain embodiments, after 180 days of storage in the dark at 30°C after formulation, the multi-phase oral compositions of the present invention comprised at least about 10% of the initial amount of hydrogen peroxide relative to the amount with which they were formulated. In certain embodiments, at least about 25% of the initial amount of hydrogen peroxide, at least about 50% of the initial amount of hydrogen peroxide, or at least about 75% of the initial amount of hydrogen peroxide may be present after 180 days of storage of the composition at 30°C. Optional stabilizing agent for the whitening agent

[0082] The multi-phase oral compositions of the present invention may comprise a stabilizing agent for the whitening agent. The whitening agent can be further stabilized against degradation by the multi-phase buccal composition. Therefore, stabilizing agents may be added to the aqueous phase of the present composition. In particular, if hydrogen peroxide is used, stabilizing agents may be added. Suitable stabilizing agents are, for example, orthophosphoric acid, phosphate(s) such as sodium hydrogen phosphate, pyrophosphate(s), organophosphonate(s), ethylenediamine tetraacetic acid, ethylenediamine-N,N'-diacetic acid, ethylenediamine acid - N,N'-disuccinic acid, potassium stannate, sodium stannate, tin salts, zinc salts, salicylic acid, 1-hydroxyethylidene-1,1-diphosphonic acid and combinations thereof. In particular, stabilizers which show additional oral treatment effects can be used, for example the anti-tartar effect, produced by pyrophosphate(s) or organophosphonate(s). In certain embodiments, a stabilizing agent may be present in a multi-phase buccal composition of the present invention in an amount from about 0.0000001%, 0.000001%, or 0.00001%, to about 0.00001%, 0.0001%, or 0.01%, by weight, of the multiphase buccal composition or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, a stabilizing agent may be present in a multi-phase buccal composition of the present invention in an amount from about 0.0001%, or 0.01% to about 0.01%, 0.1%, or about 1% by weight of the aqueous phase or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0083] A stabilizing agent may also include chelators. The chelator may be a copper, iron and/or manganese chelator, or a mixture thereof. Suitable chelators can be selected from: diethylene triamine pentacete, diethylene triamine penta(methyl phosphonic acid), ethylenediamine-N'N'-disuccinic acid, ethylenediamine tetraacetate, ethylenediamine tetra(methylene phosphonic acid), di( phosphonic methylene) and any combination thereof. A suitable chelator may be selected from ethylenediamine-N'N'-disuccinic acid (EDDS), hydroxyethane diphosphonic acid (HEDP) or mixtures thereof. The stabilizer may comprise ethylenediamine-N'N'-disuccinic acid or a salt thereof. Ethylene diamine-N'N'-disuccinic acid may be in the enantiomeric S,S form. The stabilizer may comprise disodium salt of 4,5-dihydroxy-m-benzene disulfonic acid, glutamic acid -N,N-diacetic acid (GLDA) and/or the salts of these substances, 2-hydroxy pyridine-1-oxide, Trilon P™ available from BASF, Ludwigshafen, Germany. Suitable chelators may also be carbonate crystal formation inhibitors. Suitable calcium carbonate crystal formation inhibitors can be selected from the group consisting of: 1-hydroxyethane diphosphonic acid (HEDP) as well as salts of this substance, N,N-dicarboxymethyl-2-aminopentane-1,5-dioic acid as well as salts of that substance; 2-phosphonobutane-1,2,4-tricarboxylic acid as well as salts thereof; and any combination thereof.

[0084] A stabilizer may comprise a calcium carbonate crystal growth inhibitor, such as 1-hydroxyethane diphosphonic acid (HEDP); N,N-dicarboxymethyl-2-aminopentane-1,5-dioic acid; 2-phosphonobutane-1,2,4-tricarboxylic acid; as well as salts of these substances; and any combination thereof.

[0085]A stabilizer may comprise a hydroxamate chelator. "Hydroxamate" means hydroxamic acid or a corresponding salt, for example coco hydroxamic acid (Axis House RK 853). hydrophobic phase

[0086] The present invention comprises a safe and effective amount of a hydrophobic phase. In certain embodiments, the present multi-phase oral compositions comprise a hydrophobic phase, wherein the hydrophobic phase may be present in at least or more than about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.1%, or 99.5%, by weight, of the oral composition of multiple or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0087] In certain embodiments, the hydrophobic phase may be present in at least about 95%, 96%, 97%, 98%, 99%, 99.1%, or 99.5%, by weight, of the buccal composition. multiphase or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0088] In certain embodiments, the hydrophobic phase may be in predominant proportion to the aqueous phase present in the multi-phase buccal composition. As used herein, "predominant proportion" means that the weight percent of the hydrophobic phase of the multi-phase buccal composition is in excess of the weight percent of the aqueous phase of the multi-phase buccal composition.

[0089]The hydrophobic phase can be inert or at least partially inert. The hydrophobic phase may interact, but in certain embodiments it does not or interacts only minimally with the other ingredients, such as flavors or thickeners, in the multi-phase mouthwash, including the whitening agent.

[0090] A hydrophobic phase suitable for the compositions disclosed herein may have an octanol/water separation coefficient (log Pow) greater than about 2, 3, 4, 5, or greater than about 5.5. In certain embodiments, the hydrophobic phase shows a log Pow greater than about 6 or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0091] Without being bound by theory, the dropping point or softening of the hydrophobic phase can be a factor in ensuring that the composition: 1) is adherent and does not run off the teeth or run off the application support during application or during the use; and 2) release an effective amount of the whitening agent or active agent during use. Specifically, if the dropping or softening point of the hydrophobic phase is too low, the multi-phase buccal composition may not be sticky and run off the teeth or run off the application support during application or during use. In contrast, if the dropping or softening point of the hydrophobic phase is too high, the multi-phase buccal composition may not release an effective amount of the whitening agent or active agent during use. The dropping or softening point of a suitable hydrophobic phase may range from about 40°C to about 80°C, from about 50°C to about 65°C, from about 50°C to about 65°C. 60°C or any other numerical range which is narrower and which is contained within such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention as measured in accordance with ASTM method D127-08. In certain embodiments, the dropping or softening point of the hydrophobic phase may be about 120°C, 100°C, 90°C, 85°C, 80°C, 75°C, 70°C, 60°C, 50°C, 40°C, or 30°C, at about 100°C, 90°C, 85°C, 80°C, 75°C, 70°C, 60°C, 50°C, 40° C, 30°C, or 25°C, or any other narrower numerical range and which is contained in such narrower numerical range, as if such narrower numerical ranges were expressly written in the present invention, as measured in accordance with the method ASTM D127-08.

[0092]Without being bound by theory, the consistency value of the cone penetration of the hydrophobic phase or the multi-phase buccal composition can be a factor in ensuring that the multi-phase buccal composition: 1) is adherent and does not run down the teeth or run off the application support during application or during use; and 2) release an effective amount of the whitening agent or active agent during use. Specifically, if the cone penetration consistency value of the hydrophobic phase or the multi-phase buccal composition is too high, the multi-phase buccal composition may not be adherent and run off the teeth or run off the application support during application. or during use. In contrast, if the cone penetration consistency value of the hydrophobic phase or multi-phase buccal composition is too low, the multi-phase buccal composition may not release an effective amount of the whitening agent or active agent during use. In certain embodiments, the cone penetration consistency value of the hydrophobic phase or multi-phase buccal compositions can be in the range of about 100 to about 300, preferably in the range of about 150 to about 250, and more preferably in the range of about 170 to about 200 or any other numerical range, as if such narrower numerical ranges are expressly written in the present invention, as measured in accordance with ASTM method D937-07. In certain embodiments, the cone penetration consistency value of the hydrophobic phase or multi-phase buccal composition can be about 10, 25, 50, 100, 110, 120, 130, 140, 150, 160, 170, 180 , 190, 200, 210, 220, 230, 240, 250, 300, 400, or 500, at about 25, 50, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 , 210, 220, 230, 240, 250, 300, 400, or 500 or any other numerical range which is narrower and which is contained within such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention , as measured according to ASTM method D937-07.

[0093] Without being bound by theory, for multi-phase oral compositions that comprise peroxide, the average residual concentration of peroxide from the multi-phase oral composition spread over the teeth can be a factor in ensuring that the multi-phase oral composition: 1 ) is adherent and does not come off during use; and 2) still release an effective amount of the whitening agent during use. Specifically, if the average residual peroxide concentration of the multi-phase buccal composition on a tooth surface is too low, the multi-phase buccal composition may not be adherent and may come off during use, or not release an effective amount of the whitening agent during use. the use. In certain embodiments, the average residual peroxide concentration of a multi-phase oral composition applied to teeth measured using the procedure specified herein may be about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or 225 at about 2, 5, 10, 15, 20 , 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or 225 or any other numerical range that is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, the average residual peroxide concentration of a multi-phase buccal composition applied to teeth measured using the procedure specified herein can be from about 1 to about 200, more preferably, from about 10 to about 200. 200, more preferably from about 50 to about 200, and most preferably from about 100 to about 200 or any other numerical range which is narrower and which is contained within such a wider numerical range as such narrower numerical ranges were expressly written in the present invention. Procedure for measuring the average residual peroxide concentration of a composition applied to teeth 1. Cut a circular disk (7.5 to 7.8 mm in diameter x 1.2 to 1.3 mm in thickness) out of the front surface of a human incisor tooth. Cut a circular disk (7.5 to 7.8 mm in diameter x 1.2 to 1.3 mm in thickness) out of the front surface of a human incisor tooth. Soak the tooth disc in 15 to 20 mL of water that meets USP specifications in a glass bottle for at least 24 hours. Remove the tooth disc from the water and place it on a clean paper towel with the front surface facing up. 2. Weigh 290 to 310 grams of water that meets USP specifications into a cylindrical plastic container with a screw top cap 82 to 107 mm in diameter x 106 to 108 mm in height ("Max 200 Long Cup Translucent", number of item 501 220t, available from Flacktek, Landrum, SC, USA). Preheat the water in the container with the lid tightly screwed on in a convection oven with an air temperature of 33°C to 35°C for at least 12 hours. 3. Weigh 0.04 to 0.06 grams of the composition onto the tip of a disposable lip gloss applicator ("Flocked Doe Foot Lip Gloss Applicator" made from nylon and polystyrene, purchased from Qosmedix Inc., Ronkonkoma, NY, USA, catalog number 74111). 4. Apply the composition onto the wet front surface of the tooth disc by first rolling the tip of the lip gloss applicator loaded with the composition onto the front surface of the tooth disc to transfer the composition onto the tooth disc and then spread towards the circular edge. 5. Grasp the tooth disc with tweezers. Make sure that the tweezers only touch the circular edge of the tooth disc and not the surface of the tooth disc applied with the composition. Tilt the plastic container and gently place the tooth disc in the water on the cylindrical wall of the container where the cylindrical wall and the flat bottom meet. Make sure the treated surface of the tooth disc is facing upwards away from the cylindrical wall of the container. 6. Place the cylindrical container in a roller mixer (model number TSRT9 by Techne purchased from VWR, Batavia, IL, USA, catalog number 89132-186; or item number 04750-30, purchased from Cole-Parmer Inc., Vernon Hills, IL, USA). Turn on the cylinder mixer - this gently rotates the bowl at 12 to 14 RPM. The tooth disc must remain immersed in the water and the treated surface must remain facing away from the rotating cylindrical wall. This rotating movement causes water to flow smoothly over the tooth disc, similar to the smooth movement of saliva and other liquids over teeth in the mouth. This is illustrated in Figure 12. 7. After 58 to 62 minutes have turned off the roller mixer, take a clean peroxide test strip (available from EMD Millipore Corporation, Billerica, MA, USA, vendor number 1.16974.0001; purchased from to VWR, Batavia, IL, USA, catalog number EM1.16974.0001) of the container, and start a timer. 8. Obtain a digital image of the peroxide test strip. The configuration of the equipment and system used to digitally image the test strip are specified in the present invention. A digital image of the sample is shown in Figure 13. 9. Remove the tooth disc from the water with forceps. As before, make sure that the tweezers only touch the circular edge of the tooth disc and not the surface of the tooth disc applied with the composition. Place the disc on the tip of a gloved finger. Make sure the surface of the tooth disc applied with the composition is facing up away from the gloved fingertip. 10. Place the peroxide test strip against the tooth disc so that one of the reaction zones contacts the surface of the tooth disc with the residual composition. Squeeze the peroxide test strip against the tooth disc between your thumb and forefinger and apply firm finger pressure between your thumb and forefinger for 2 to 3 seconds. 11. Move the peroxide test strip to a clean area of a paper towel. Place a filter paper (Whatman standard grade 1 qualitative filter paper, circle, 90 mm, supplier number 1001-090; purchased from VWR, Batavia, IL, USA, catalog number 28450 - 081) over the test strip. Apply pressure with your fingers on the filter paper. Pull the peroxide test strip from below the filter paper (while maintaining finger pressure on the filter paper) in a single stroke so that excess gel is removed by the filter paper and paper towel. Make sure the reaction zones do not dislodge from the peroxide test strip. 12. Obtain a digital image of the peroxide test strip. The configuration of the equipment and system used to digitally image the test strip are specified in the present invention. A digital image of the sample is shown in Figure 13. 13. Steps 7 to 12 must be completed within the 3 minutes indicated on the timer. 14. Repeat steps 1 through 13 for a minimum of twelve teeth. 15. Use Adobe Photoshop CS4 with the procedure specified here to measure the mean and standard deviation of the RED intensities of the Munsell N8 matte color sheet tape attached to the holder that serves as an internal reference for Munsell N8 within each image. The average RED intensity of the Munsell N8 internal reference within each image must be 204 to 212 and the standard deviation must not be greater than 3. 16. Use Adobe Photoshop CS4 with the procedure specified here to measure the average of the intensities of RED from the reaction zone on all peroxide test strips in the REFERENCE (before pressing against the disc). 17. Use the Adobe Photoshop CS4 program with the procedure specified here to measure the average of the RED intensities of the same reaction zone on all peroxide test strips AFTER pressing against the tooth disc 18. The average residual peroxide concentration of a composition applied to the teeth is calculated as follows: First, calculate the baseline mean intensity of RED from each reaction zone from step 16 MINUS the mean intensity of RED from the same reaction zone after pressing with the residual composition over the tooth disc from step 17. Repeat this calculation for all reaction zones pressed against the tooth disc and average the results. This is the average residual peroxide concentration of a composition applied to teeth.

[0094] In certain embodiments, the density of the hydrophobic phase used in the multi-phase oral compositions of the present invention ranges from about 0.8 g/cm3 to about 1.0 g/cm3, from about 0.85 g/cm3 to about 0.95 g/cm3, or about 0.9 g/cm3, or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0095] In certain embodiments, the hydrophobic phase may be a non-toxic oil, such as a non-toxic edible oil. In certain embodiments, the hydrophobic phase may include non-toxic edible oils, saturated or unsaturated fatty alcohols, aliphatic hydrocarbons, long chain triglycerides, fatty esters, and mixtures thereof. In certain embodiments, the hydrophobic phase may also comprise silicones, polysiloxanes and mixtures thereof. In certain embodiments, the hydrophobic phase may be selected from mineral oil, in particular petrolatum and mixtures thereof, more preferably petrolatum, for example white petrolatum, is used as the hydrophobic phase of the present composition. Examples of petrolatum include Snow White Pet - C available from Calumet Specialty Products (Indianapolis, IN, USA), G-2191 available from Sonneborn (Parsippany, NJ, USA), G-2218 available from Sonneborn, G-1958 available from Sonneborn, G-2180 available from Sonneborn, Snow White V28 EP available from Sonneborn and Snow White V30 available from Sonneborn and mixtures thereof.

[0096] In certain embodiments, the aliphatic hydrocarbons can contain from about 10, 12, 14 or 16 to about 16, 18, 20, 22, 24, 26, 28, 30, 36, 40 carbon atoms such as decane, 2-ethyldecane, tetradecane, isotetradecane, hexadecane, eicosane and mixtures thereof. In certain embodiments, the long chain triglycerides can include vegetable oils, fish oils, animal fats, hydrogenated vegetable oils, partially hydrogenated vegetable oils, semi-synthetic triglycerides, synthetic triglycerides and mixtures thereof. In certain embodiments, fractionated, refined or purified oils of these types may also be used. In certain embodiments, examples of oils containing long chain triglycerides include almond oil; babassu oil; borage oil; black currant seed oil; canola oil; Castor oil; coconut oil; corn oil; cottonseed oil; emu oil; oil of Primula; linseed oil; grape seed oil; peanut oil; mustard seed oil; olive oil; Palm oil; palm kernel oil; peanut oil; rapeseed oil; safflower oil; Sesame oil; shark liver oil; soy oil; Sunflower oil; hydrogenated castor oil; hydrogenated coconut oil; hydrogenated palm oil; hydrogenated soybean oil; hydrogenated vegetable oil; a mixture of hydrogenated cottonseed oil and hydrogenated castor oil; partially hydrogenated soybean oil; a mixture of partially hydrogenated soybean oil and partially hydrogenated cottonseed oil; glyceryl trioleate; glyceryl trilinoleate; glyceryl trilinolenate; an oil containing polyunsaturated fatty acid triglyceride Q3; and mixtures thereof. The oils containing long-chain triglycerides may in particular be selected from the group consisting of corn oil, olive oil, palm oil, peanut oil, safflower oil, sesame oil, soybean oil, castor oil , linseed oil, rapeseed oil, rice bran oil, coconut oil, hydrogenated castor oil; partially hydrogenated soybean oil; glyceryl trioleate; glyceryl trilinoleate; an oil containing polyunsaturated fatty acid triglyceride Q3; and mixtures thereof.

[0097] In certain embodiments, suitable saturated or unsaturated fatty alcohols have from about 6 to about 20 carbon atoms, cetearyl alcohol, lauryl alcohol and mixtures thereof. For example, Lipowax (cetearyl alcohol and Cetearet-20) are supplied and produced by Lipo Chemical.

[0098] General information on silicones, including silicone fluids, gums and resins, as well as the manufacture of silicones, can be found in the "Encyclopedia of Polymer Science and Engineering", Volume 15, second edition, pages 204 to 308, John & Wiley Sons Inc. 1989 and Chemistry and Technology of Silicones, Walter Noll, Academic Press Inc., (Harcourt Brue Javanovich, Publishers, New York, USA), 1968, pages 282-287 and 409-426.

[0099] The multi-phase buccal composition as disclosed herein may comprise additional ingredients, which may optionally be added, and which will be described in more detail below.

[0100] The multi-phase oral compositions of the present invention may comprise an emulsifier. Surprisingly, in certain embodiments, a multi-phase buccal composition can be formed even when no emulsifier is used. Without being bound by theory, it is believed that the low amount of aqueous phase, combined with the rheological properties, flow properties, dropping or softening point and/or cone penetration consistency of the hydrophobic phase, and/or the process of preparation of the composition can help disperse the aqueous phase in the hydrophobic phase and keep it dispersed without the use of an emulsifying agent. Accordingly, the present multistage bleaching oral compositions are preferably substantially free of ingredients that may compromise effectiveness, wear experience, concentration of active ingredients or bleaching agents on the surface of teeth over time. , the effectiveness of the active ingredient or lightening agent, or the compatibility between ingredients, for example an emulsifier. The term "substantially free of an emulsifier", as understood in the present invention, means that the composition comprises less than 0.001% by weight of an emulsifier. More preferably, the present multi-phase whitening mouthwash compositions are free of an emulsifier, i.e., they do not comprise any emulsifier.

[0101] In certain embodiments, the multi-phase oral compositions may comprise from about 0.001% to 30% of an emulsifier. Any emulsifier can be used as long as the emulsifier chosen is non-toxic to a user. In certain embodiments, an emulsifier (or a combination of emulsifiers) favors the formation of a multi-phase buccal composition. In certain embodiments, the present multi-phase oral compositions may comprise from about 0 to about 0.1%, from about 0.1 to about 5%, from about 0.1 to about 3%, or from about 0.5% to about 1.5% by weight of the emulsifier multi-phase buccal composition.

[0102] Classes of surfactants useful as emulsifiers include nonionic, anionic, cationic, amphoteric, synthetic emulsifying agents and mixtures thereof. Many suitable nonionic and amphoteric surfactants are disclosed in US Patent No. 3,988,433; in US Patent No. 4,051,234, and many suitable nonionic surfactants are also disclosed in US Patent No. 3,959,458.

[0103] In certain embodiments, since multi-phase oral compositions are favored with more lipophilic emulsifiers, the emulsifier may have a hydrophilic-lipophilic balance (HLB) value of from about 1 to about 10, an HLB value from about 3 to about 8, an HLB value from about 4 to about 7, or an HLB from about 4 to about 6. A single emulsifier or a combination of emulsifiers can be used. In certain embodiments, the emulsifier may be a mixture of two or more emulsifiers, such as a blend of two or more non-ionic emulsifiers. In this sense, an emulsifier that tends to form a multi-phase buccal composition and an emulsifier that forms an oil-in-water emulsion can be mixed together to achieve the HLB required for a multi-phase buccal composition (HBL values are algebraically additive). ).

[0104] Other emulsifiers also useful in the present invention include natural emulsifying agents such as acacia, gelatin, lecithin and cholesterol; finely dispersed solids such as colloidal clays, bentonite, veegum (magnesium aluminum silicate; and synthetic emulsifying agents such as fatty acid salts, sulfates such as sorbitan trioleate, sorbitan tristearate, sucrose distearate, propylene glycol monostearate, glycerol monostearate , propylene glycol monolaurate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene-4-lauryl ether, sodium lauryl sulfate, sulfonates such as sodium dioctyl sulfosuccinate, glyceryl esters, polyoxyethylene glycol esters and ethers, diethylene glycol monostearate, diethyl distearate PEG 200 and fatty acid esters of sorbitan such as sorbitan monopalmitate, and polyoxyethylene derivatives thereof, polyoxyethylene glycol esters such as monostearate, polysorbate 80 (ethoxylated sorbitan monooleate) (supplied by Spectrum, etc.); and mixtures thereof .

[0105] An emulsifier can be a surfactant that is unreactive with a whitening agent. For example, surfactants that are not reactive with a bleaching agent have no hydroxyl groups, are free of nitrogen groups and bonds, are essentially free of metals like Zn, etc.

[0106]The emulsifier may be a non-ionic surfactant. Nonionic surfactants include polyoxyethylene sorbitan fatty acid esters such as materials sold under the Tween trademark. The number after the "polyoxyethylene" part in the following section refers to the total number of oxyethylene groups -(CH2CH2O)- found in the molecule. The number after the "polysorbate" part refers to the type of fatty acid associated with the polyoxyethylene sorbitan part of the molecule. Monolaurate is indicated by 20, monopalmitate is indicated by 40, monostearate is indicated by 60, and monooleate is indicated by 80. Examples of such materials are polyoxyethylene (20) sorbitan monolaurate (Tween 20), polyoxyethylene (20) sorbitan monopalmitate ( Tween 40), polyoxyethylene (20) sorbitan monostearate (Tween 60), polyoxyethylene (4) sorbitan monostearate (Tween 61), polyoxyethylene (20) sorbitan tristearate (Tween 65), polyoxyethylene (20) sorbitan monooleate ( Tween 80), polyoxyethylene (5) sorbitan monooleate (Tween 81) and polyoxyethylene (20) sorbitan trioleate (Tween 85), and mixtures thereof. Polyoxyethylene fatty acid esters are also suitable and examples include those materials sold under the trademark Myrj such as polyoxyethylene (8) stearate (Myrj 45) and polyoxyethylene (40) stearate (Myrj 52), and mixtures thereof. Other nonionics also include polyoxyethylene-polyoxypropylene block polymers such as poloxamers and Pluronics.

[0107] Another suitable class of nonionic surfactants for optional use in the present invention are polyoxyethylene fatty ethers, such as materials commercially available under the trademark Brij. Examples of such materials are polyoxyethylene (4) lauryl ether (Brij 30), polyoxyethylene (23) lauryl ether (Brij 35), polyoxyethylene (2) cetyl ether (Brij 52), polyoxyethylene (10) cetyl ether (Brij 56), polyoxyethylene (20) cetyl ether (Brij 58), polyoxyethylene (2) stearyl ether (Brij 72), polyoxyethylene (10) stearyl ether (Brij 76), polyoxyethylene (20) stearyl ether (Brij 78) , polyoxyethylene (2) oleic ether (Brij 93), polyoxyethylene (10) oleic ether and polyoxyethylene (20) oleic ether (Brij 99), and mixtures thereof.

[0108]A portion of a non-ionic surfactant may be substituted for a lipophilic surfactant, such as sorbitan fatty acid esters, such as materials sold under the Arlacel trademark. Suitable lipophilic surfactants include sorbitan monolaurate (Arlacel 20), sorbitan monostearate (Arlacel 60), sorbitan monooleate (Arlacel 80), sorbitan sesquioleate (Arlacel 83) and sorbitan trioleate (Arlacel 85), and mixtures of the same. Suitable lipophilic surfactants include sorbitan monolaurate (Arlacel 20), sorbitan monostearate (Arlacel 60), sorbitan monooleate (Arlacel 80), sorbitan sesquioleate (Arlacel 83) and sorbitan trioleate (Arlacel 85), and mixtures of the same.

[0109] In certain embodiments, the emulsifier may be Aerosol OT (Sodium Dioctyl Sulphosuccinate) produced by Cytec.

[0110]Furthermore, in certain embodiments, multi-phase oral compositions may also be substantially free of ingredients that could compromise effectiveness, user experience, concentration of active ingredients or whitening agents on the tooth surface while over time, the effectiveness of the active ingredient or lightening agent, or the compatibility between ingredients, eg acids and/or alcohols. In certain embodiments, the multi-phase buccal compositions may comprise less than 0.001%, by weight, of the composition, acids and/or alcohols, preferably, the multi-phase buccal compositions do not comprise acids and/or alcohols. Without sticking to theory, it is believed that the decrease in surface tension produced by alcohol can decrease the retention time of the aqueous phase on the dental surface, thus decreasing the effectiveness of active ingredients for oral treatment. The presence of acids can counteract the active ingredients and/or can produce negative side effects on the dental surface such as hypersensitivity, etc. Thus, in certain embodiments, the present multi-phase oral compositions are preferably acid-free, alcohol-free, or a mixture thereof. In certain embodiments, the hydrophobic phase of the multi-phase oral composition may be substantially free of ingredients that could compromise the effectiveness, wear experience, concentration of active ingredients or whitening agents on the tooth surface over time, efficiency. of the active ingredient or the lightening agent, or the compatibility between the ingredients, for example the lightening agent. In certain embodiments, the multi-phase oral composition may be substantially free of ingredients that may compromise efficacy, user experience, concentration of active ingredients or whitening agent on the tooth surface over time, active ingredient efficiency, or the bleaching agent, or the compatibility between the ingredients, for example, pyrolyzed silica, polyorganosiloxanes, copolymer condensation products of silicone resins and polydiorganosiloxanes, solid ingredients, or combinations thereof. In certain embodiments, the multi-phase buccal composition may be substantially free of pyrolyzed silica as this can decrease the stability of the bleaching agent, especially if the bleaching agent is in a liquid form or dissolved in a liquid. Additional Ingredients of Multi-Phase Mouth Composition Thickening agents, viscosity modifiers, or particulate fillers

[0111] The multi-phase oral compositions of the present invention may comprise a safe and effective amount of a thickening agent, a viscosity modifier, or particulate fillers. A thickening agent may also provide acceptable rheology to the composition. The viscosity modifier can further function as an inhibitor of settling and component separation, or control said settling in order to facilitate redispersion and can control the flow properties of the composition. In addition, a thickening agent or viscosity modifier can facilitate the use of the present compositions with suitable delivery devices, such as dental tapes, films, or trays, by increasing retention on the surfaces of the delivery devices. The thickening agent, as described herein, can also serve as an adhesive.

[0112] When present, a thickening agent, viscosity modifier or particulate filler may be present in a content of from about 0.01% to about 99%, from about 0.1% to about 50%, from about from 1% to about 25%, or from about 1% to about 10%, by weight of the multiphase buccal composition.

[0113] Suitable thickening agents, viscosity modifiers, or particulate fillers that can be used in the present invention include modified clays, silicas, synthetic polymers such as cross-linked siloxanes, cellulose derivatives (e.g., methyl cellulose, carboxymethyl cellulose, hydroxy ethyl cellulose, hydroxy propyl cellulose, hydroxypropylmethyl cellulose, etc.), carbomer polymers (e.g., copolymer or homopolymer of cross-linked polyacrylic acid and copolymers of acrylic acid cross-linked with a polyalkenyl polyether), natural and synthetic gums, karaya gum, guar gum, gelatin , algin, sodium alginate, tragacanth, chitosan, polyethylene oxide, acrylamide polymers, polyacrylic acid, polyvinyl alcohol, polyamines, polyquaternary compounds, ethylene oxide polymers, polyvinylpyrrolidone, cationic polyacrylamide polymers, waxes (which include paraffin wax and microcrystalline waxes), polyethylene, pyrolyzed silica, polymetac rylates, olefin copolymers, hydrogenated styrene-diene copolymers, styrene polyesters, rubber, polyvinyl chloride, nylon, fluorocarbon, polyurethane prepolymer, polyethylene, polystyrene, alkylated polystyrene, polypropylene, cellulosic resins, acrylic resins, elastomers, poly(n-butyl vinyl ether), poly(styrene-co-maleic), poly(covinyl acetate, alkyl fumarate), poly(t-butyl styrene) and mixtures thereof.

[0114]Examples of polyethylene include A-C 1702 or A-C 6702 produced by Honeywell Corp. (Morristown, NJ, USA), with a penetration value of about 98.5 and about 90.0, respectively, according to ASTM D1321; Performalene polyethylene series available from Baker Hughes; this includes Performalene 400 polyethylene available from Baker Hughes Inc. (Houston, TX, USA). Examples of microcrystalline wax include the Multiwax series available from Sonneborn (Parsippany, NJ, USA), Crompton (Witco); these include Multiwax 835, Multiwax 440, Multiwax 180 and mixtures thereof.

[0115] Examples of polymethacrylates include, for example, polyacrylate-co-methacrylate, polymethacrylate-costyrene or combinations thereof. Examples of elastomers include, for example, hydrogenated styrene-co-butadiene, hydrogenated styrene-co-isoprene, ethylene-ethylene-propylene polymer, ethylene-propylene polymer, styrene-ethylene-ethylene-propylene-styrene polymer or combinations of the above. same. An example of a rubber includes hydrogenated polyisoprene. Other examples of viscosity modifiers can be found in "Chemistry and Technology of Lubricants," Chapman and Hall (2nd edition 1997).

[0116]Suitable carbomers comprise the class of acrylic acid homopolymers cross-linked with an alkyl ether of pentaerythritol or an alkyl ether of sucrose. Carbomers are commercially available from B.F. Goodrich as the Carbopol® series, eg Carbopol 934, 940, 941, 956 and mixtures thereof. Polyacrylic acid homopolymers are described, for example, in US Patent No. 2,798,053. Other examples of homopolymers that are useful include Ultrez 10, ETD 2050 and 974P polymers, which are available from B.F. Goodrich Company (Greenville, SC, USA). Such polymers are homopolymers of unsaturated polymerizable carboxylic monomers such as acrylic acid, methacrylic acid, maleic acid, itaconic acid, maleic anhydride and the like. Optional additional active agents for oral care

[0117] The composition of the present invention may comprise a safe and effective amount of an active agent for additional oral care, such as any material that is generally considered safe for use in the oral cavity and that provides changes in the appearance or general health of the oral cavity. Additional active ingredients suitable for oral care include one or more anti-tartar agents, fluoride ion sources, antimicrobial agents, dentin desensitizing agents, anesthetic agents, antifungal agents, anti-inflammatory agents, selective H-2 antagonists, anticaries agents, nutrients, erythritol, probiotics and mixtures thereof.

[0118] The additional active agent for oral care may contain an active ingredient in a content at which, upon recommended use, the benefit sought by the user is promoted without prejudice to the oral surface to which said active ingredient is applied. Examples of the oral conditions these active ingredients provide include, but are not limited to, changes in the appearance and structure of teeth, stain removal, plaque removal, tartar removal, caries prevention and treatment, inflamed and/or bleeding gums. , mucosal wounds, lesions, ulcers, aphthous ulcers, canker sores, tooth abscesses and elimination of unpleasant mouth odor resulting from the above diseases and other causes such as microbial proliferation. In certain embodiments, the content of the additional active ingredient for oral care that can be used in the multi-phase oral compositions can be from about 0.01% to about 50%, from about 0.1% to about 20% , from about 0.5% to about 10%, or from about 1% to about 7%, by weight, of the multiphase buccal composition or any other numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0119]In certain modalities, the additional active agent for oral care may be a healing agent that promotes or enhances the healing or regenerative process. In certain embodiments, such healing agents may comprise hyaluronic acid or salts, glucosamine or salts, allantoin, curcumin, D-panthenol, niacinamide, ellagic acid, flavonoids (including fisetin, quercetin, luteolin, apigenin), vitamin E, ubiquinone or mixtures of the same.

[0120] In certain embodiments, the additional active agent for oral care may be one or more probiotics selected from Lactobacillus reuteri ATCC 55730; Lactobacillus salivarius strain TI12711 (LS 1); Lactobacillus paracasei ADP-1; Streptococcus salivarius K12; Bifidobacterium DN-173010; L. paracasei strain filtrate (pro-t-action™); S. oralis KJ3, S. rattus JH145, S. uberis KJ2; Lactobacillus reuteri Prodentis; Lactobacillus salivarius LS1; Lactobacillus paracasei; Lactobacillus paracasei ADP1; Streptococcus salivarius M18, K12 or BLIS K12 and BLIS M18; Bacillus amyloliquefaciens; Bacillus clausii; Bacillus coagulans; Bacillus subtilis; Bacillus subtilis: E-300; Bifidobacterium animalis; Bifidobacterium B6; Bifidobacterium bifidum; Bifidobacterium breve (Bb-03); Bifidobacterium DN-173010; Bifidobacterium GBI 30 6068; Bifidobacterium infantil; Bifidobacterium lactis; Bifidobacterium lactis Bb-12; Bifidobacterium longum; Bifidobacterium thermophilum; Enterococcus faecalis; Enterococcus faecium; Enterococcus faecium NCIMB 10415; Enterococcus LAB SF 68; Lactobacilli reuteri ATCC 55730 and ATCC PTA 5289; Lactobacilli reuteri ATCC 55730 and ATCC PTA 5289 (10:1); Lactobacillus acidophilus; Lactobacillus acidophilus ATCC 4356 and Bifidobacterium bifidum ATCC 29521; Lactobacillus acidophilus; Bifidobacterium longum; Bifidobacterium bifidum; Bifidobacterium lactis; Lactobacillus brevis; Lactobacillus casei (Ssp. Casi); Lactobacillus casei Shirota; Lactobacillus confusus; Lactobacillus crispatus YIT 12319; Lactobacillus curvatus; Lactobacillus delbrueckii ssp. Bulgaricus PXN 39; Lactobacillus fermentum; Lactobacillus fermentum YIT 12320; Lactobacillus gasseri; Lactobacillus gasseri YIT 12321; Lactobacillus helveticus; Lactobacillus johnsonii; Lactobacillus kimchii; Lactobacillus lactis L1A; Lactobacillus paracasei (Lpc37); Lactobacillus paracasei GMNL-33; Lactobacillus pentosus; Lactobacillus plantarum; Lactobacillus plantarum; Lactobacillus protectus; Lactobacillus reuteri; Lactobacillus reuteri ATCC 55730; Lactobacillus reuteri SD2112 (ATCC55730); Lactobacillus rhamnosus (GG); Lactobacillus rhamnosus GG; Lactobacillus rhamnosus GG; L. rhamnosus LC705; Propionibacterium freudenreichii ssp; Shermanii JS; Lactobacillus rhamnosus L8020; Lactobacillus rhamnosus LB21; Lactobacillus salivarius; Lactobacillus salivarius WB21; Lactobacillus sporogenes; Lactococcus lactis Ssp. Diacetylactis; Lactococcus lactis Ssp. lactis; Pediococcus acidilactici; Pediococcus pentosaceus; Saccharomyces boulardii; Saccharomyces cerevisiae; strep. uberis KJ2sm; strep. oralis KJ3sm; strep. rattus JH145; Streptococcus mitis YIT 12322; Streptococcus oralis KJ3; Streptococcus rattus JH145; Streptococcus salivarius (BLIS K12 or BLIS M18); Streptococcus salivarius K12; Streptococcus thermophilus; Streptococcus uberis KJ2; Thermus thermophiles; Weissella cibaria CMS2; Weissella cibaria CMS3; and Weissella cibaria CMU.

[0121]Probiotics can be used in the multi-phase oral compositions of the present invention to promote positive oral health effects such as reducing caries and plaque, promoting gum health, improving breath, promoting whitening. In certain embodiments, the effectiveness of probiotics in multi-phase oral compositions can be determined by measuring one or more of the following: reduction in levels of mutans salivary streptococci; reduction of gingival crevicular fluid; reduction of periodontal pathogens (C. rectus and P. gingivitis) in the subgingival plaque; lower yeast counts; lower prevalence of oral candida; reduction of the oral contents of volatile sulfur compounds (VSC); and reduced production of TNF-α and IL-8. Without being bound by theory, it is believed that one or more of the aforementioned positive oral health effects can be achieved through the production of bacterial toxins, which remove or reduce certain types of bacteria in the oral cavity; additionally, one or more of the above positive oral health effects can be achieved through bacterial production of one or more enzymes that inhibit the production of or dissolve/loosen the biofilms or sticky deposits, which can lead to oral health problems.

[0122] As the present multi-phase oral composition is directed at whitening the dental surface and removing or diminishing the stains affixed thereto, in certain embodiments, a safe and effective amount of at least one anti-tartar agent can be added to the compositions as herein. revealed. In certain embodiments, said amount may be from about 0.01% to about 40%, from about 0.1% to about 25%, from about 4.5% to about 20%, or from about 5% to about 15% by weight of the multiphase buccal composition, or any other numerical range which is narrower and which is contained within such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. The anti-tartar agent may also be compatible with the other components of the multi-phase buccal composition, in particular the whitening agent. The anticaking agent can be selected from the group consisting of polyphosphates as well as salts of these substances; polyamino propanesulfonic acid (AMPS) as well as salts of these substances; polyolefin sulfonates and salts thereof, polyvinyl phosphates and salts thereof, polyolefin phosphates and salts thereof, diphosphonates and salts thereof, phosphonoalkane carboxylic acid and salts thereof, polyphosphonates and salts thereof, polyvinyl phosphonates as well as salts of these substances, polyolefin phosphonates as well as salts of these substances, polypeptides and mixtures thereof, said salts generally being alkali metal salts. In certain embodiments, the anti-scaling agents used in the present multi-phase buccal composition also show a stabilizing effect for bleaching agents such as pyrophosphates, polyphosphates, polyphosphonates and mixtures thereof.

[0123]For example, the anti-tartar agent may be a polyphosphate. It is generally understood that a polyphosphate comprises two or more phosphate molecules arranged primarily in a linear configuration, although some cyclic derivatives may be present. Linear polyphosphates correspond to (X PO 3 )n, where n is from about 2 to about 125, preferably n is greater than 4 and X is, for example, sodium, potassium and the like. For (X PO3)n when n is at least 3, polyphosphates are glassy in character. The counterions for these phosphates can be an alkali metal, alkaline earth metal, ammonium, C2-C6 alkanolammonium and mixtures of salts. Polyphosphates are generally used in the form of their fully or partially neutralized water-soluble alkali metal salts, such as potassium, sodium, ammonium salts and mixtures thereof. Inorganic polyphosphate salts include alkali metal (e.g. sodium) tripolyphosphate or tetrapolyphosphate, dialkyl metal diacid (e.g. disodium), trialkyl metal monoacid (e.g. trisodium), potassium hydrogen phosphate, sodium hydrogen phosphate, hexametaphosphate alkali metal (e.g. sodium) and mixtures thereof. Polyphosphates larger than tetrapolyphosphate usually occur as amorphous glassy materials such as those produced by the FMC Corporation which are commercially known as Sodaphos (n«6), Hexaphos (n«13), Glass H (n«21) and mixtures thereof. . If present, the present compositions will typically comprise from about 0.5% to about 20%, in particular from about 4% to about 15%, and more specifically from about 6% to about 12% % by weight of the polyphosphate composition.

[0124] Pyrophosphate salts useful in the present compositions include: alkali metal pyrophosphates, di-, tri-, and monopotassium or sodium pyrophosphates, di-alkali metal pyrophosphate salts, tetra-alkali metal pyrophosphate salts, and mixtures thereof. For example, the pyrophosphate salt is selected from the group consisting of trisodium pyrophosphate, disodium dihydrogen pyrophosphate (Na2H2P2O7), dipotassium pyrophosphate, tetrasodium pyrophosphate (Na4P2O7), tetrapotassium pyrophosphate (K4P2O7) and mixtures thereof, with tetrasodium pyrophosphate is preferred. The tetrasodium pyrophosphate may be in anhydrous salt or decahydrate form, or any other species stable in solid form in the present compositions. The salt is in the form of solid particles, which may be in their crystalline and/or amorphous state, with the particle size of the salt preferably being small enough to be aesthetically acceptable and readily soluble in use. The pyrophosphate salt content in the present compositions can be from about 1.5% to about 15%, in particular from about 2% to about 10%, and more specifically from about 3% to about 8% by weight of the composition.

[0125]Phosphate sources, including but not limited to polyphosphates and pyrophosphates, are described in more detail in "Kirk & Othmer, Encyclopedia of Chemical Technology", Fourth Edition, Volume 18, Wiley-Interscience Publishers (1996), pages 685 to 707, incorporated herein by reference in its entirety, all incorporated references to said work by Kirk & Othmer being included.

[0126]Polyolefin phosphonates include those in which the olefin group contains 2 or more carbon atoms. Polyvinyl phosphonates include polyvinyl phosphonic acid. Diphosphonates as well as salts of this substance include azocycloalkane-2,2-diphosphonic acids as well as salts of this substance, ions of azocycloalkane-2,2-diphosphonic acids as well as salts of this substance (such as those in which the alkane moiety has five, six or seven carbon atoms, where the nitrogen atom is unsubstituted or bears a lower alkyl substituent, e.g. methyl), azacyclohexane-2,2-diphosphonic acid, azacyclopentane-2,2-diphosphonic acid, N-methyl acid -azacyclopentane-2,3-diphosphonic acid, EHDP (ethane hydroxy-1,1,-diphosphonic acid), AHP (azacycloheptane-2,2-diphosphonic acid, also known as 1-azocycloeptylidene-2,2-diphosphonic acid) , ethane-1-amino-1,1-diphosphonate, dichloromethane-diphosphonate, etc. The phosphonoalkane carboxylic acid or alkali metal salts of this substance include PPTA (phosphonopropane tricarboxylic acid), PBTA (phosphonobutane-1,2,4-tricarboxylic acid), each as acid or alkali metal salts.

[0127] In addition, antimicrobial antiplaque agents may also be present in the present compositions. These antimicrobials may include, but are not limited to, triclosan, 5-chloro-2-(2,4-dichlorophenoxy)-phenol, as described in the Merck Index, 11th edition (1989), page 1529 (entry no. 9573), in US Patent No. 3,506,720 and European Patent Application No. 0,251,591; chlorhexidine (Merck Index, no. 2090); alexidine (Merck Index, no. 222); hexetidine (Merck Index, no. 4624); sanguinarine (Merck Index, no. 8320); benzalkonium chloride (Merck Index, no. 1066); salicylanilide (Merck Index, no. 8299); domiphene bromide (Merck Index, no. 3411); cetylpyridinium chloride (CPC) (Merck Index, no. 2024); tetradecylpyridinium chloride (CTP); N-tetradecyl-4-ethylpyridinium chloride (CTDEP); octenidine; delmopinol, octapinol and other piperidino derivatives. In addition, there may be antimicrobially effective amounts of essential oils and combinations thereof, for example, citral, geranial, and combinations of menthol, eucalyptol, thymol, and methyl salicylate; antimicrobial metals as well as salts of these substances, for example those that provide zinc ions, stannous ions, copper ions and/or mixtures thereof; bisbiguanides, or phenolics; antibiotics such as aumentin, amoxicillin, tetracycline, doxycycline, minocycline and metronidazole; and analogs and salts of the aforementioned antiplaque and/or antifungal antimicrobial agents, such as those for the treatment of Candida albicans. If present, these agents will generally be in a safe and effective amount, for example, from about 0.1% to about 5%, by weight, of the present compositions.

[0128] In addition, the present composition may comprise a safe and effective amount of an anticaries agent, and mixtures thereof. The anticaries agent can be selected from the group consisting of xylitol, a fluoride ion source that provides free fluoride ions and mixtures thereof. In certain embodiments, a suitable fluoride ion source may be selected from the group consisting of sodium fluoride, stannous fluoride, indium fluoride, organic fluorides such as amine fluorides, and sodium monofluorophosphate, with sodium fluoride being preferred. In certain embodiments, preferably, the present compositions can provide from about 50 ppm to 10,000 ppm, more preferably, from about 100 to 3000 ppm of fluoride ions in the compositions that come in contact with dental surfaces when used with the composition of the present invention.

[0129] In addition, cooling agents, desensitizing agents, and anesthetic agents may be used as optional ingredients in compositions of the present invention, in particular, at a content of about 0.001% to about 10%, more specifically, from about 0 .1% to about 1% by weight of the composition. Cooling agents, desensitizers and anesthetics can decrease potential negative perceptions such as tingling, burning, etc. The coolant can be any one of a wide variety of materials. Included among these materials are carboxamides, menthol, ketals, diols and mixtures thereof. Optional cooling agents in the present compositions may be paramentane carboxamide based agents such as N-ethyl-p-menthane-3-carboxamide (known as "WS-3"), N,2,3-trimethyl-2-isopropylbutanamide (known as "WS-23"), menthol, 3-1-menthoxy propane-1,2-diol (known as TK-10), menthone glycerol acetal (known as MGA), menthyl lactate (known as Frescolat®) and blends of the same. The terms menthol and mentyl, as used herein, include dextrorotatory and levorotatory isomers of these compounds and racemic mixtures thereof. Desensitizing or anti-pain agents may include, but are not limited to, strontium chloride, potassium nitrate, natural herbs such as gall nut, mite, cubebin, galangal, scutellaria, Liangmianzhen (Zanthoxylum nitidum), Baizhi (Angelica dahurica), etc. Suitable anesthetic agents include benzocaine, lidocaine, clove bud oil and ethanol.

[0130] In addition, anti-inflammatory agents may be present in the multi-phase oral compositions disclosed herein. These agents may include, but are not limited to, non-steroidal anti-inflammatory agents such as aspirin, ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, ketoprofen, piroxicam and meclofenamic acid, COX-2 inhibitors such as valdecoxib, celecoxib and rofecoxib , and mixtures thereof. If present, anti-inflammatory agents generally comprise from about 0.001% to about 5% by weight of the compositions.

[0131]Furthermore, nutrients such as minerals can improve teeth and tooth surface and thus can be included with compositions as disclosed herein. Suitable minerals are, for example, calcium, phosphorus, fluoride, zinc, manganese, potassium and mixtures thereof. These minerals are disclosed, for example, in "Drug Facts and Comparisons" (brochure drug information service), available from the Wolters Kluer Company, St. Louis, MO, USA, ©1997, pages 10 to 17.

[0132] In addition, the compositions of the present invention may also contain a safe and effective amount of a flavoring agent. Suitable flavoring agents include wintergreen, peppermint, peppermint, clove bud, menthol, anethole, methyl salicylate, eucalyptol, 1-menthyl acetate, sage, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaetol, cinnamon, vanillin, thymol, linalool, cinnamaldehyde glycerol acetal known as CGA, and mixtures thereof. If present, flavoring agents are generally used at levels of from about 0.01% to about 30%, in particular from about 1% to about 20%, more particularly from about 1. 5% to about 15% by weight of the composition.

[0133] In addition, the present compositions may optionally comprise sweetening agents, including sucralose, sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcones, salts of acesulfame and cyclamate, especially sodium cyclamate and sodium saccharin, and mixtures thereof. If present, the composition contains from about 0.1% to about 10% of such agents, in particular, from about 0.1% to about 1%, by weight, of the composition.

[0134] In addition, colorants, pigments, dyes and mixtures thereof may optionally be included in the present composition to give the compositions of the present invention a colored appearance. An advantage of adding pigments and/or dyes to the compositions of the present invention is that they will enable the user to see if the composition evenly and completely covers their teeth, as it is easier to visualize coverage with a colored composition. In addition, the dye can provide color similar to the color of whitened teeth. Dyes useful in the present invention are stable with the bleaching agent and are those known to be safe. The contents of colorants, pigments and dyes which are optionally used in the present invention range from about 0.05% to about 20%, in particular from about 0.10% to about 15%, and more specifically , from about 0.25% to about 5% by weight of the composition.

whitening effectiveness

[0135]In certain embodiments, the whitening efficacy of the present invention, measured according to clinical protocol, as disclosed herein and calculated as -Δb*, may be at least about 0.25, 0.5, 1, 1 ,5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9 or 10 or any other numerical range which is narrower and which is contained within such wider numerical range, as if such wider numerical ranges narrow lines were expressly written in the present invention.

[0136] In certain embodiments, the whitening efficacy of the present invention, measured in accordance with the clinical protocol as disclosed herein, and calculated as -Δb*, may be at least about 0.25, preferably at least about 0.25. 0.5, more preferably at least about 1.0, even more preferably at least about 1.5, even more preferably at least about 2, most preferably at least about 2.5, with more preferably at least about 3, even more preferably at least about 3.5, and most preferably at least about 4, or any other narrower numerical range and which is contained within such narrower numerical range, as if such narrower numerical ranges were expressly written in the present invention. Generally speaking, a change in yellowing, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, of at least 0.25 is noticeable.

[0137] The present invention has been found to provide a surprisingly high ratio between the whitening efficacy of the present invention, measured in accordance with the clinical protocol as disclosed herein, and calculated as of -Δb* and the weight percentage of bleaching agent. whitening present in the total multi-phase oral composition.

[0138]In certain embodiments, the ratio of the whitening efficacy of the present invention, measured in accordance with the clinical protocol as disclosed herein, and calculated as -Δb*, and the percentage by weight of the whitening agent present in the total of the The multiphase buccal composition can be at least about 0.25, 0.5, 1, 1.5, 2, 2.5, 5, 10, or 15 or any other numerical range that is narrower and that is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0139]In certain embodiments, the ratio of the whitening effectiveness of the present invention, measured in accordance with the clinical protocol as disclosed herein, and calculated as -Δb*, and the percentage by weight of whitening agent present in the total composition The multiphase mouthpiece may be at least about 2.5, preferably at least about 5, more preferably at least about 10, most preferably at least about 15.

[0140]In certain embodiments, the whitening efficacy of the present invention, measured according to clinical protocol as disclosed herein, and calculated as -Δb* may be at least about 10%, at least about 100%, at least about 1000%, or at least about 10,000% more than the whitening effectiveness of a comparative oral care composition in the form of an aqueous solution or aqueous gel. The comparative oral care composition comprises the same whitening agent at the same general concentration dissolved in the aqueous solution or aqueous gel.

[0141] The present invention was found to have: 1) a surprisingly high ratio of bleaching efficacy, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting irritation buccal or was observed to have buccal irritation that was possible or likely to be attributed to the composition tested; 2) a surprisingly high ratio of the whitening efficacy of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb* treatments, and the fraction of participants who reported tooth sensitivity that was possible or likely to be attributed to the composition ; or 3) a surprisingly high ratio of the bleaching efficacy of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants who reported tooth sensitivity or reported oral irritation or were observed to have oral irritation that was possible or likely to be attributed to the composition.

[0142]In certain embodiments, the ratio of the whitening efficacy of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting tooth sensitivity that is possible or likely to be attributed to the present invention may be at least about 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100 or any other numerical range which is narrower and which is contained within such a wider numerical range as if such narrower numerical ranges were expressly written in the present invention.

[0143]In certain embodiments, the ratio of the whitening effectiveness of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting tooth sensitivity that is possible or likely attributed to the present invention may be at least about 6, preferably at least about 7, more preferably at least about 8, even more preferably at least about 9, most preferably at least about 10, with even more preferably at least about 15, even more preferably at least about 20, even more preferably at least about 25, and most preferably at least about 50, or any other numerical range that is narrower and is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0144]In certain embodiments, the ratio of the whitening efficacy of the present invention measured in accordance with the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting oral irritation or observed to have oral irritation which is possible or likely to be attributed to the present invention may be at least about 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100 or any other numerical range which is narrower and which is contained in such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0145]In certain embodiments, the ratio of the whitening efficacy of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting oral irritation or having oral irritation which is possible or likely to be attributed to the present invention may be at least about 6, preferably at least about 7, more preferably at least about 8, most preferably at least about 9, most preferably at least about 9 at least about 10, even more preferably at least about 15, even more preferably at least about 20, even more preferably at least about 25, and most preferably at least about 50, or any other range narrower numerical range and which is contained in such narrower numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0146]In certain embodiments, the ratio of the whitening effectiveness of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting tooth sensitivity or reporting oral or irritation was observed to have mouth irritation that is possible or likely to be attributed to the present invention may be at least about 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100 or any other numerical range that is narrower and that is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention.

[0147]In certain embodiments, the ratio of the whitening effectiveness of the present invention, measured according to the clinical protocol as disclosed herein, and calculated as -Δb*, and the fraction of participants reporting tooth sensitivity or reporting oral or irritation has been observed to exhibit buccal irritation which is possible or likely to be attributed to the present invention may be at least about 6, preferably at least about 7, more preferably at least about 8, most preferably at least about 9, even more preferably at least about 10, even more preferably at least about 15, even more preferably at least about 20, even more preferably at least about 25, and even more preferably at least about 50 , or any other narrower numerical range, as if such narrower numerical ranges were expressly written in the present invention.

clinical protocol

[0148] The whitening efficacies of multi-stage oral compositions are measured using the following clinical protocol. Per treatment group, 17 to 25 participants are recruited to complete the clinical study when testing compositions with less than about 1% whitening agent and 8 to 25 participants when testing compositions with at least about 1% whitening agent. whitening. Recruited participants must have four natural maxillary incisors with all measurable facial sites. The average L* reference of the participant group should be 71 to 76, and the average reference b* of the participant group should be 13 to 18. In addition, participants with malocclusion in the anterior maxillary teeth, severe or atypical intrinsic staining , such as that caused by tetracycline, fluorosis or hypocalcification, dental crowns or restorations over the facial surfaces of maxillary anterior teeth, self-reported medical history of melanoma, current smoking or tobacco use, sensitivity to light, or a skin pigmentation disorder, Self-reported tooth sensitivity, or prior whitening of teeth using a professional treatment, over-the-counter kit, or investigational product, are excluded from the study. Participants are provided with travel kits containing Crest Cavity Protection Toothpaste and Soft Oral-B Indicator Manual Toothbrush (both obtained from Procter & Gamble, Cincinnati, OH, USA) to be used twice daily in the usual manner.

[0149] Participants use a toothbrush ("Anchor 41 tuft white toothbrush" obtained from Team Technologies, Inc. Morristown, TN, USA) to brush their teeth with water for 30 seconds prior to treatment with the multiple mouthwash composition. phases. Each participant's anterior maxillary teeth are treated with the multi-phase oral composition for 60 minutes once daily, using a polyethylene tape as an application support. Polyethylene tapes are 66mm x 15mm in size and 0.0178mm thick. From 0.6 g to 0.8 g of the multi-phase buccal composition is applied to each polyethylene strip prior to application to the maxillary anterior teeth.

[0150]If the multi-phase buccal composition is used with electromagnetic radiation: 1) After 50 minutes of treatment with the multi-phase buccal composition on the tape, the electromagnetic radiation is applied towards the facial surfaces of the maxillary anterior teeth for 10 minutes, 2) Electromagnetic radiation is directed to the maxillary anterior teeth through the tape and through the multi-phase buccal composition, 3) The tape must allow at least about 90% of the electromagnetic radiation from 400 nm to 500 nm to pass through it , and 4) Electromagnetic radiation is delivered through four fiber optic cables (model number M71L01 available from Thorlabs, Newton, NJ, USA) connected to four high power LEDs with a wavelength with peak intensity of 455 nm (model number M455F1 available from Thorlabs, Newton, NJ, USA), as shown in Figure 6. The four LEDs run at 1000 mA, each using a trigger and a LED hub (model numbers DC4104 and DC4100-HUB obtained from Thorlabs, Newton, NJ, USA). The output ends of the four fiber optic cables are mounted behind a clear mouthpiece to help reproducibly position electromagnetic radiation against the outer surface of the tape. The exit ends of the four fiber optic cables are approximately 7 mm away from the exit surface of the mouthpiece with electromagnetic radiation passing through the transparent mouthpiece. The mouthpiece bite holder is offset so that the transparent window through which electromagnetic radiation passes towards the maxillary anterior teeth is 7.4 mm high. In addition, the transparent window through which electromagnetic radiation passes towards the maxillary anterior teeth is 40 mm in length measured linearly from end to end (excluding curvature). The output ends of the fiber optic cables are positioned and angled so that the cones of electromagnetic radiation exiting the fiber optic cables are centered inside the transparent window through which the electromagnetic radiation passes towards the maxillary anterior teeth, as shown in Fig. shown in Figure 6. In addition, the outgoing ends of the four fiber optic cables are spaced so that the cones of electromagnetic radiation are spaced along the length of the transparent window through which the electromagnetic radiation passes towards the maxillary anterior teeth. , as shown in Figure 6. The intensity of electromagnetic radiation from 400 nm to 500 nm measured on the central axis of each cone of electromagnetic radiation exiting the exit surface of the transparent window through which the electromagnetic radiation passes towards the maxillary teeth above, needs to be about 175 mW/cm2 at about 225 m W/cm2 as measured by the method disclosed herein.

[0151]Once the 60 minute treatment with the multi-phase oral composition is over, the tape is removed. This treatment is applied once daily for a minimum of 7 days for compositions with less than about 1% lightening agent, and a minimum of 3 days for compositions with at least about 1% lightening agent.

[0152] The change in tooth color due to treatment with the multi-phase oral composition is measured using the procedure described below the day after the 7th treatment for compositions with less than about 1% whitening agent and thereafter of the 3rd treatment for compositions with at least about 1% bleaching agent.

[0153]Tooth color is measured using a digital camera that has a lens equipped with a polarizing filter (camera model no. CANON EOS 70D available from Canon Inc., Melville, NY, USA, with a NIKON lens 55mm micro-NIKKOR with adapter). The lighting system is provided by Dedo Lights (model number DLH2) equipped with 24 V, 150 watt lamps (model number Xenophot HL X64640), positioned at a distance of 30 cm from each other (measured from the center of the surface outer ring of one of the glass lenses through which the light comes out to the other) and directed at a 45 degree angle so that the light paths intersect in the vertical plane of the chin rest about 36 cm in front of the camera's focal plane. Each light has a polarization filter (Lee 201 filter) and a cutoff filter (Rosco 7 mil Thermashield filter available from Rosco, Stamford, CT, USA).

Grade de padrão de cor 2

Grade de padrão de cor 3

[0154] At the intersection of the light paths, a fixed chin rest is mounted for reproducible repositioning in the light field. The camera is placed between the two lighting fixtures so that its focal plane is approximately 36 cm from the vertical plane of the chin rest. The camera is placed between the two lighting fixtures so that its focal plane is approximately 36 cm from the vertical plane of the chin rest. A gray Munsell N8 pattern is imaged first. The camera's white balance is adjusted so that the gray RGB values are 200. Color patterns are imaged to obtain standard RGB values from the color chips. The color standards and the gray standard are mentioned below (available from Munsell Color, X-rite Division, Grand Rapids, MI, USA). Each color pattern is identified with the Munsell nomenclature. To create a grid of color patterns, they can be arranged as follows. This makes it possible for multiple color patterns to be contained in a single image captured from the color pattern grid. color pattern grid 1

color pattern grid 2

3 color pattern grid

[0155]For the reference tooth color, participants use a toothbrush ("Anchor 41 tuft white toothbrush" available from Team Technologies, Inc. Morristown, TN, USA) to brush their teeth with water to remove debris from your teeth. Each participant then uses cheek retractors (available from Washington Scientific Camera Company, Sumner, WA, USA; matte-finished from A&B Deburring Company, Cincinnati, OH, USA) to pull the cheeks back and allow the surfaces facial features of the teeth are illuminated. Each participant is instructed to bite down on their teeth so that the incisal edges of the maxillary incisors come into contact with the incisal edges of the mandibular incisors. Participants are then positioned on the chin rest at the intersection of light paths in the center of the camera's view and images of the teeth are captured. After all participants have been imaged, the images are processed using image analysis software (Optimas produced by Media Cybernetics, Inc. of Silver Spring, MD, USA). The four central incisors are isolated and the mean RGB values of the teeth are extracted.

[0156]After the participants have used a whitening product, but before capturing the images of the participant's teeth, the system is adjusted to the reference setting and calibrated as previously discussed. After calibration, each participant is imaged a second time using the same procedure as before, making sure that the participant is in the same physical position as the pre-treatment image including teeth orientation. The images are processed using the image analysis program to obtain the average RGB values of the four central maxillary incisors. The RGB values of all images are then mapped into the CIE L*'a*b* color space using the RGB values and L*a*b* values of the color chips over the color standard. . The L*a*b* values of the color chips in the color standard are measured using a Photo Research SpectraScan PR650 instrument, available from Photo Research Inc., LA, USA, using the same lighting conditions described for capturing digital images of the facial dentition. The PR650 equipment is positioned at the same distance from the color standards and the camera. Each chip is individually measured for L*a*b* assessment after calibration, according to the manufacturer's instructions. The RGB values are then transformed into L*a*b* values using regression equations such as: L* = 25.16 + 12.02*(R/100) + 11.75*(G/100) — 2.75*(B/100) + 1.95*(G/100)3 a* = -2.65 + 59.22*(R/100) -50.52*(G/100) + 0 .20*(B/100)- 29.87*(R/100)2 + 20.73*(G/100)2 + 8.14*(R/100)3- 9.17(G/100) 3 + 3.64*[(B/100)2]*[R/100] b* = -0.70 + 37.04*(R/100) + 12.65*(G/100) - 53, 81*(B/100) - 18.14*(R/100)2 + 23.16*(G/100)*(B/100) + 4.70*(R/100)3 - 6.45* (B/100)3 The R2 for L*, a*, and b* must be > 0.95. Each study must have its own equations.

[0157]These equations are, in general, valid transformations in the area of tooth color (60 < L* < 95, 0 < a* < 14.6 < b* < 25). The data from each participant's image set is then used to calculate the product's bleaching performance in terms of changes in L*, a* and b*- a standard method used to assess bleaching benefits. When evaluating compositions with less than about 1% bleaching agent: Changes in L* are defined as ΔL* = L*day after 7 treatments — L*reference where a positive change indicates improvement in gloss; Changes in a* (balance between green and red) are defined as Δa* = a*day after 7 treatments - a*baseline where a negative change indicates teeth that are less red; Changes in b* (balance between blue and yellow) are defined as Δb* = b*day after 7 treatments - b*reference where a negative change indicates teeth that are becoming less yellow. When evaluating compositions with at least about 1% bleaching agent: Changes in L* are defined as ΔL* = L*after 3 treatments - L*reference where a positive change indicates improvement in gloss; Changes in a* (balance between green and red) are defined as Δa* = a*after 3 treatments - a*baseline where a negative change indicates teeth that are less red; Changes in b* (balance between yellow and blue) are defined as Δb* = b*after 3 treatments - b*reference where a negative change indicates teeth that are becoming less yellow. -Δb* is used as the main measure of whitening effectiveness. The overall color change is calculated by the equation of ΔE = (ΔL*2 + Δa*2 + Δb*2) 1/2.

[0158]After using the whitening products, the color changes in the CIE Lab color space can be calculated for each participant based on the equations provided.

[0159]To validate the above clinical protocol, the whitening efficacy (calculated as -Δb*) of Example IA (provided on a tape and used with electromagnetic radiation as disclosed herein) needs to be measured on the day after the 7th treatment and demonstrated be >0.5. Optional application systems

[0160]Furthermore, the present invention may further refer to a delivery system for applying the present compositions to the dental surface. For example, in certain embodiments, the compositions of the present invention can provide whitening benefits to the oral cavity when applied directly to teeth without the use of an application carrier system. Furthermore, in certain embodiments, the present invention may include a delivery system comprising the present compositions in combination with an application support. For example, the delivery system may comprise a first layer of a support material and a second layer comprising a multi-phase buccal composition described herein, such that the whitening agent is releasably located in the present composition. A suitable first layer may comprise an application support which includes a tape of material, a dental tray, a sponge material and mixtures thereof. In certain embodiments, the application support may be a tape of material, such as a permanently deformable tape. Suitable tapes of material or suitable permanently deformable tapes are, for example, disclosed in US Patent Nos. 6,136,297; 6,096,328; 5,894,017; 5,891,453; and 5,879,691; and US Patent Nos. 5,989,569 and 6,045,811; and in US patent application 2014/0178443 A1.

[0161]The application support can be fixed to the teeth through attachment means that are part of the application support, for example, the application support can be of sufficient size so that, once applied, it overlaps the soft tissues of the oral cavity making more of the tooth surface available for whitening. The delivery support can also be attached to the oral cavity through physical interference or mechanical interlocking between the delivery support and the buccal surfaces, including the teeth.

[0162]The application support can be transparent or translucent to electromagnetic radiation with wavelengths from about 200 nm to about 1,700 nm. In certain embodiments, the application support enables about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%, 80%, 90%, or 100% of the electromagnetic radiation of about from 400 nm to about 500 nm passes through it.

[0163] When the application support is a tape material, the composition of the second layer can be applied as a coating over the tape, or be applied by the user to the tape, or be applied by the user to the teeth, and then the tape can be be placed over coated teeth. The amount of composition applied to the tape or teeth may depend on the size and capacity of the tape, the concentration of active ingredient and the desired benefit; for example, from about 0.0001, 0.001 or 0.01 gram to about 0.01, 0.1, 1, or 5 grams may be used or any other numerical range which is narrower and which is contained in such wider numerical range, as if such narrower numerical ranges were expressly written in the present invention, of the composition, in particular from about 0.001 g to about 0.5 g or from about 0.1 g to about 0.4 g of the multi-phase buccal composition may be used. In addition, from about 0.0001, 0.001, or 0.01 gram to about 0.01, 0.1, 0.5, or 1 gram of composition per square centimeter of material (g/cm 2 ) can be used or any other narrower numerical range and which is contained within the wider numerical range, as if such narrower numerical ranges were expressly written in the present invention; in certain embodiments less than about 0.2 g/cm2, from about 0.0001 g/cm2 to about 0.1 g/cm2, or from about 0.01 g/cm2 to about 0.04 g /cm2. In addition, or alternatively, from about 1 microgram to about 5,000 micrograms of bleaching agent per square centimeter of material (microgram/cm2 ), preferably from about 10 micrograms/cm2 to about 500 micrograms/cm2 , and more preferably, from about 50 micrograms/cm2 to about 100 micrograms/cm2 of bleaching agent per square centimeter of material may be used.

[0164] Referring now to the drawings, and more particularly to Figure 1, there is shown an embodiment of a suitable delivery system 10, which represents a delivery system for applying whitening actives provided by a multi-phase oral composition, as disclosed herein, to the teeth and oral cavity. The delivery system 10 comprises a material in the form of tape 12 of material that is substantially flat, and may have rounded corners. On said tape 12 a second layer 14 comprising the present multi-phase buccal composition is releasably applied. The second layer 14 may be homogeneous and may be evenly and evenly spread over the tape 12, as shown in the cross-sectional view of Figure 2. In addition, the second layer 14 comprising the present compositions may be a coating only along a longitudinal axis of a portion of the tape of material 12 or may be applied as bands, dots and/or other patterns. However, in certain embodiments, the second layer 14 may be a laminate or separate layers of components, an amorphous mixture of components, separate stripes or dots or other patterns of different components, or a combination of these structures including a coating of the second layer 14 along with along a longitudinal axis of a portion of a tape of material 12.

[0165] In certain embodiments, the second layer 14 may contain, or is itself, an active ingredient, such as a composition, compound or mixture, capable of influencing or effecting a desired change in the appearance or structure of the surface with the which contact. As discussed above, examples of active ingredients include: hydrogen peroxide, carbamide peroxide, sodium fluoride, sodium monofluorophosphate, pyrophosphate, chlorhexidine, polyphosphate, triclosan and enzymes. Examples of appearance and structural changes include, but are not necessarily limited to: bleaching, stain lightening, stain removal, remineralization to form fluorapatite, plaque removal, and tartar removal.

[0166] In addition, the composition of the second layer 14 may comprise adhesive means for stably affixing the delivery system 10 to the dental surface. In certain embodiments, the composition as disclosed herein can provide the desired tack and adhesion on its own, for example, by choosing a hydrophobic phase that already provides adhesive properties, by adding adhesive material to the compositions of the present invention, or both. In certain embodiments, if added, an adhesive may provide additional properties, such as thickening/rheology-modifying properties.

[0167] Figures 3 and 4 show a delivery system 10 of the present invention applied to the dental surface of a plurality of adjacent teeth. Embedded in adjacent soft tissues 20 is a plurality of adjacent teeth 22. Adjacent soft tissues 20 of the present invention are defined as the soft tissue surfaces that surround the tooth structure, including: papilla, marginal gingiva, gingival sulcus, interdental gingiva and structure. from the gingival gingival on the lingual and buccal surfaces up to and including the mucogingival junction on the pallet.

[0168] In both Figures 3 and 4, the release system 10 represents a tape 12 and a second layer 14 comprising the present composition, the second layer 14 being situated on the side of the material tape 12 facing the teeth 22. The composition of the second layer 14 can be pre-applied to the tape of material 12, or it can be applied to the tape of material 12 by the wearer prior to application to the teeth. Alternatively, the composition of the second layer 14 can be applied directly to the teeth 22 by the user and then covered by a tape 12. In any case, the tape of material 12 can have a thickness and a flexural rigidity that makes it possible to adapt to it. the curvilinear surfaces of the teeth 22 and adjacent soft tissues 20. In this way, the tape of material 12 can have sufficient flexibility to conform to the contours of the buccal surface, the surface being a plurality of adjacent teeth 22. The tape 12 may also be readily conformable to the dental surfaces and interstitial spaces of the teeth without permanent deformation when the release system 10 is applied. The release system 10 can be applied without significant pressure.

[0169] The first layer 12 of the release system 10 may be comprised of a tape of material. Such first layer materials are described in more detail in US Patent Nos. 6,136,297; 6,096,328; 5,894,017; 5,891,453; and 5,879,691; and US Patent Nos. 5,989,569 and 6,045,811; and in US patent application 2014/0178443 A1. Tape 12 serves as a protective barrier to the whitening agent in the second layer 14. This prevents leaching or erosion of the second layer 14, for example, by the user's tongue, lips and saliva. This enables the active agent in the second layer 14 to act on the dental surfaces 22 of the buccal cavity for the intended period of time, for example from several minutes to several hours.

[0170] The following description of material tape may apply to release systems 10 with the tape layer 12 shown in Figures 1 to 4 or any form of tapes. The material tape may comprise polymers, natural and synthetic fabric materials, non-woven materials, foil, paper, rubber and combinations thereof. The tape of material may be a single layer of material, or a laminate comprising more than one layer. Regardless of the number of layers, the tape of material can be substantially water-insoluble. The material tape may also be waterproof. Suitable tape material is any type of polymer or combination of polymers which has the required flexural rigidity and which is compatible with oral care substances. Suitable polymers include, but are not limited to, polyethylene, ethyl vinyl acetate, polyesters, ethyl vinyl alcohol and combinations thereof. Examples of polyesters include Mylar® and fluoroplastics like Teflon®, both produced by DuPont. In certain embodiments, the material used as the material tape is polyethylene. The tape of material may be less than about 1 mm thick, preferably less than about 0.05 mm thick, or from about 0.001 to about 0.03 mm thick. A polyethylene tape of material can be less than about 0.1 mm thick or from about 0.005 to about 0.02 mm thick.

[0171] In certain embodiments, the present invention may comprise a dissolvable film, which can be adhered to the oral cavity thereby releasing an active, wherein the dissolvable film comprises water-soluble polymers, one or more polyalcohols, and one or more ingredients active. In addition to one or more active ingredients, a dissolvable film may contain a combination of certain plasticizers or surfactants, colorants, sweetening agents, flavors, flavor enhancers, or other excipients commonly used to modify the flavor of formulations intended for application to the oral cavity. . The resulting dissolvable film is characterized by an instantaneous wettability which causes the dissolvable film to soften soon after application to the mucosal tissue, thus preventing the wearer from experiencing any prolonged adverse sensation in the mouth, and a tensile strength suitable for operations. normal coating, cutting, tearing and packing.

[0172] The dissolvable film may comprise a water-soluble polymer or a combination of water-soluble polymers, one or more plasticizers or surfactants, one or more polyalcohols, and an active ingredient.

[0173]Polymers used for the dissolvable film include polymers that are hydrophilic and/or water dispersible. Examples of polymers that can be used include polymers that are water-soluble cellulose derivatives, such as hydroxypropyl methyl cellulose, hydroxyethyl cellulose, or hydroxypropyl cellulose, alone or mixtures thereof. Other optional polymers, without limiting the invention, include polyvinylpyrrolidone, carboxy methyl cellulose, polyvinyl alcohol, sodium alginate, poly(ethylene glycol), natural gums such as xanthan gum, tragacanth, guar gum, acacia gum, gum arabic, water-dispersible polyacrylates such as polyacrylic acid, methyl methacrylate copolymer, carboxy vinyl copolymers. The concentration of the water-soluble polymer in the final film can vary between 20 and 75% (w/w), or between 50 and 75% (w/w).

[0174] The surfactants that can be used for the dissolvable film can be one or more non-ionic surfactants. When a combination of surfactants is used, the first component may be a polyoxyethylene sorbitan fatty acid ester or an ALPHA-hydro-OMEGA-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer, while the second component it can be a polyoxyethylene alkyl ether or a polyoxyethylene castor oil derivative. In certain embodiments, the HLB value of the polyoxyethylene sorbitan fatty acid ester must be between 10 and 20, so that a range of 13 to 17 can also be used. The ALPHA-hydro-OMEGA-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer can contain at least about 35 oxypropylene units and, in certain embodiments, not less than about 50 oxypropylene units.

[0175]Polyoxyethylene alkyl ether may have an HLB value between 10 and 20 and, in certain embodiments, an HLB value of not less than 15 may be used. The polyoxyethylene castor oil derivative can have an HLB value of 14 to 16.

[0176]To obtain the desired instantaneous wettability, the ratio between the first and the second component of the binary surfactant mixture can be maintained between 1:10 and 1:1, or between 1:5 and 1:3.

[0177] The total concentration of surfactants in the dissolvable film depends on the properties of the other ingredients, but, in general, it can be between 0.1 and 5% (w/w).

[0178]Polyalcohol can be used to achieve a desired level of dissolving film softness. Examples of polyalcohols include glycerol, poly(ethylene glycol), propylene glycol, monoesters of glycerol with fatty acids or other pharmaceutically used polyalcohols. The concentration of polyalcohol in the dry film is usually in the range between 0.1 and 5% (w/w).

[0179] The material tape shape can be any shape or size that covers the desired buccal surface. For example, in certain embodiments, the tape of material may have rounded corners to avoid irritation of the soft tissues of the oral cavity. "Rounded corners," as used herein, means not having any sharp angles or points, for example, one or more angles of 135° or less. The length of the material tape can be from about 2 cm (centimeters) to about 12 cm, or from about 4 cm to about 9 cm. The width of the tape of material may also depend on the buccal surface area to be covered. The width of the material tape can be from about 0.5 cm to about 4 cm or from about 1 cm to about 2 cm. The tape of material can be used as a plaster over one or several teeth to treat a localized condition.

[0180]The material ribbon may contain shallow cavities. When the multi-phase oral composition is applied as a coating over a tape of material, whitening agents and/or oral care active ingredients fill the shallow cavities to provide reservoirs of additional whitening agents and/or oral care active ingredients. Additionally the shallow cavities help to provide a texture to the delivery system. The material tape may have an array of shallow cavities. Generally speaking, shallow cavities are approximately 0.4 mm across and 0.1 mm deep. When shallow cavities are included in the material tape and the multi-phase oral compositions of the present invention are applied thereto in various thicknesses, the total thickness of the delivery system is less than about 1 mm, in particular, the total thickness is less. than about 0.5 mm.

[0181]Bending stiffness is a material property that is a function of a combination of the thickness and width of the material tape and the material's modulus of elasticity. This test described below is a method for measuring the stiffness of films such as a polyolefin film and sheets. It determines the flexural strength of a sample using a strain gauge attached to the end of a horizontal bar. The opposite end of the bar presses along a strip of the sample, to force a portion of the same in a vertical groove existing in a horizontal platform on which the said sample is placed. A microammeter, wired to the strain gauge, is calibrated in terms of deflection force. Sample stiffness is read directly from the microammeter and expressed as grams per centimeter of sample tape width. In certain embodiments, a tape of material that is suitable for use as an application support for the compositions of the present invention may have a flexural stiffness of less than about 5 g/cm, as measured on a Handle-O-Meter. Model No. 211-300, available from Thawing-Albert Instrument Company of Philadelphia, PA, USA, per ASTM Test Method D2923-95. The tape may have a flexural stiffness of less than about 3 g/cm, less than about 2 g/cm, or a flexural stiffness of about 0.1 to about 1 g/cm. Generally speaking, the flexural stiffness of the tape material can be substantially constant and does not change during normal use. For example, the material tape does not need to be hydrated for the tape to achieve the low flexural stiffness in the ranges specified above. This relatively low stiffness allows the material tape to cover the contours of the buccal surface with very little force being exerted. That is, adaptation to the contours of the wearer's buccal surface is maintained, as there is little residual force on the material tape to return it to its shape prior to application to the buccal surface, i.e., substantially flat. For example, in certain embodiments, the flexibility of a tape of material enables it to contact soft tissue for an extended period of time without causing irritation; so that a tape of material does not require pressure to hold against the buccal surface.

[0182] Delivery systems, as used herein, may comprise an adhesion means so that they are capable of adhering to oral surfaces, especially teeth. Such a means of adhesion may be provided by the present compositions or the adhesion medium may be provided independently of the compositions of the present invention (e.g. the adhesion medium is a separate phase from the compositions of the present invention wherein the compositions may also have a sticker). In certain embodiments, the tape of material may be held in place on the buccal surface by the adhesive attachment provided by the present composition. The viscosity and general tackiness of the emulsion to dry surfaces can cause the tape of material to be adhesively attached to the buccal surface without substantial slipping from the frictional forces created by the lips, teeth, tongue and other buccal surfaces rubbing against the buccal surface. material tape when talking, drinking, etc. However, this adhesion to the buccal surface must be low enough to allow the material tape to be easily removed by the user by simply removing the material tape with the use of the user's finger. The delivery system is easily removable from the oral surfaces without the use of an instrument, a solvent or chemical agent, or excessive friction.

[0183]Furthermore, in certain embodiments the material tape may be held in place on the buccal surface by adhesive means and attachment provided by the application support itself. For example, the material tape can stretch, fix, and adhere to the oral soft tissues. Additionally, in certain embodiments, an adhesive may be applied to the portion of the tape of material that will secure the delivery systems to the oral soft tissues. The delivery support can also be attached to the oral cavity through physical interference or mechanical interlocking between the delivery support and the buccal surfaces, including the teeth. Furthermore, the tape of material can be held in place by an adhesion means that is independent of the composition of the present invention, as disclosed in WO 03/015656.

[0184] Suitable adhesion means are known to the person skilled in the art. When the adhesive means, if present, is provided by an adhesive, the adhesive can be any that can be used to adhere materials to the surface of the teeth or to a surface of the surfaces of the buccal cavity. Suitable patches include, but are not limited to, skin, gum, and mucus patches, and must be able to withstand moisture, chemicals, and enzymes from the oral environment long enough for the active oral care ingredients and/or bleaching agents take effect, but may be soluble and/or biodegradable thereafter. Suitable adhesives may comprise, for example, water-soluble polymers, hydrophobic and/or water-insoluble polymers, pressure- and moisture-sensitive adhesives, for example, adhesives that become tacky on contact with the oral environment, e.g. e.g. under the influence of moisture, chemicals or enzymes, etc. in the mouth. Suitable adhesives include natural gums, synthetic resins, natural or synthetic rubbers, the gums and polymers mentioned above under "Thickening Agents", and various other tacky substances of the type used in known adhesive tapes, those known from U.S. Patent No. 2,835 .628.

[0185] The application support, such as a tape, as shown, for example, in Figures 1 to 4, can be formed by several of the film production processes known in the art. For example, a polyethylene tape is made by a blowing process or a molding process. Other processes, including extrusion or processes that do not affect the flexural stiffness of the tape material are possible as well. In addition, the present compositions which form a second layer on the tape may be incorporated onto the tape during processing thereof and/or the present composition may be a layer laminated on the tape. The second layer secured to the tape of that delivery system, as disclosed above, comprises a safe and effective amount of the present composition described herein.

[0186] In addition, the release system may comprise an optional release liner. The release liner may be formed from any material that exhibits less affinity for the second layer composition than the second layer composition does for itself and the tape of first layer material. The release liner may comprise a rigid sheet of material such as polyethylene, paper, polyester or other material which is then coated with a non-stick type material. The release liner can be cut to substantially the same size and shape as the material tape or the release liner can be cut larger than the material tape to provide a readily accessible means of separating the material from the tape. The release liner can be formed from a brittle material that cracks when the band is flexed, or from multiple pieces of material or a marked piece of material. Alternatively, the release liner can be in two overlapping pieces like a typical adhesive bandage design. A description of materials suitable as release agents is found in the "Kirk-Othmer Encyclopedia of Chemical Technology", Fourth Edition, Volume 21, pages 207 to 218, incorporated herein by reference.

[0187] In certain embodiments, the application support may be a tape of permanently deformable material that has a strength limit and a thickness such that the tape of material substantially conforms to the shape of a tooth upon permanent deformation under pressure. less than about 250,000 Pascals, as it has been discovered that users will press a tape over each tooth using the tip of a finger with a surface area of about one square centimeter. They typically apply force to each tooth for one second or less with a typical application pressure in the range of about 100,000 Pascals to about 250,000 Pascals.

[0188] In certain embodiments, a tape of material has viscoelastic properties that allow it to slide as well as flex to fit over various teeth and around the arch of the wearer's mouth. It is important that the required permanent deformation occurs under a minimum normal force applied by the user.

[0189]The multi-phase buccal composition can also be applied to the surface of the teeth and can be covered with the deformable tape before or after it has been shaped. Additionally or alternatively, the multi-phase buccal composition may be applied to the deformable tape as a precoat and may be applied along with the tape to the surface of the teeth before or after the deformable tape has been shaped, the tape being applied so that when the delivery system is placed on a tooth surface, the multi-phase buccal composition contacts the tooth surface delivering an active ingredient to the tooth surface. In addition or alternatively, the tape of deformable material can be applied to the teeth with sufficient force to conform to the shape of the application support so that it at least partially conforms to the shape of the teeth, the oral care composition can be applied to the Shaped material tape and the formatted material tape can be reapplied to the tooth surface so that it at least partially conforms to a tooth shape and brings the oral care composition into contact with the tooth surface. If the deformable tape is applied together with the multi-phase buccal composition to the tooth surface, the multi-phase buccal composition may also comprise adhesive agents to hold the delivery system in place for a period of time sufficient to allow the active ingredient of the multi-phase oral composition acts on the surface. The multi-phase buccal composition, if used in conjunction with a deformable tape, may have sufficient extrusion strength to withstand a normal force applied to mold the tape of deformable material so that substance is not substantially extruded from the space between the tape of deformable material. deformable material and the surface when manually formatting the deformable material tape. The term "substantially extruded from" means that at least 50% or more of the multiphase buccal composition is extruded from the space between the strip of deformable material and the tooth and adjacent soft tissue surfaces.

[0190]Deformable material tape can be produced from a permanently deformable material, such as wax, putty, tin or foil, as a single layer or a combination of layers or materials, such as a laminate. In certain embodiments, the deformable tape may be wax, such as sheet wax #165 formulated and manufactured by Freeman Mfg. & Supply Co. of Cleveland, Ohio, USA. This specific wax readily adapts to the shape of a tooth under a pressure of about 133,000 Pascals, which is the pressure generated when the wearer applies a normal force of about 1.36 kg (about 3 pounds) over an area of about of a square centimeter. The tape of deformable material may have a nominal film thickness of about 0.8 mm, with the deformable tape being substantially flat and rectangular in shape with rounded corners. The tape of deformable material may be of sufficient length to cover a plurality of adjacent teeth while conforming to the curvature of the wearer's mouth and the gaps between adjacent teeth. If the strip of deformable material includes the multi-phase buccal composition applied as a coating thereon, the multi-phase buccal composition may have an overall thickness of less than about 1.5 mm. The deformable tapes as disclosed herein may also be used as the material for the tape of material 12 shown in Figures 1 to 4. Thus, the general characteristics of a tape of material as described above, for example with reference to Figures 1 to 4, can also be applied to the tape of deformable material. In addition, a release liner and/or shallow cavities can also be combined with a tape of deformable material.

[0191] Alternatively, the present compositions may be used in combination with an application support that includes a dental tray and/or foam material. Dental trays are well known in the whitening art and an example of dental tray 30 is shown in Figure 5. The general process for preparing dental trays 30 is known in the art. Dentists have traditionally used three types of dental appliances for teeth whitening.

[0192] The first type is a rigid appliance that is precisely adjusted to the patient's dental arches. For example, an alginate impression that records all dental surfaces plus the gingival margin is made and an impression is readily produced from the impression. If reservoirs are desired, they are prepared by building a layer of rigid material over the mold onto specific surfaces of the teeth to be treated. A dental tray is then vacuum formed from the modified mold using conventional techniques. Once formed, the tray is preferably trimmed flush with the gingival margin on both the buccal and lingual surfaces. Sufficient tray material should be left to ensure that the entire tooth will be covered with an accuracy of about M to about ^mm from the gingival edge when finishing and beveling the periphery of the tray. A curved cutout can be made over and around the interdental papillae so that the finished tray does not cover them. All edges of the tray are preferably smoothed so that the lips and tongue do not feel a prominent edge. The resulting tray provides a perfect fit of the patient's teeth, optionally with reservoirs or spaces situated where the rigid material has been placed in the impression. Dental trays may comprise soft transparent vinyl material that has a preformed thickness of from about 0.1 cm to about 0.15 cm. Soft material is more comfortable for the patient to wear. A harder material (or thicker plastic) can also be used to build the tray.

[0193] A second type of rigid custom dental appliance is an "oversized" rigid custom dental appliance. The fabrication of rigid, customized dental appliances involves making mold models of the patient's dental arch impressions, and heating and vacuum forming a thermoplastic sheet corresponding to the mold models of a patient's dental arches. Thermoplastic films are sold in rigid or semi-rigid sheets, and are available in various sizes and thicknesses. The dental lab fabrication technique for the oversized rigid dental appliance involves augmenting the facial surfaces of the teeth in the mold models with materials such as a matrix spacer or light cured acrylics. Next, the thermoplastic laminate is heated and subsequently vacuum formed around the augmented mold models of the dental arch. The net effect of this method results in an "oversized" custom rigid dental appliance.

[0194] A third type of less frequently used custom rigid dental appliance is a custom rigid bilaminate dental appliance manufactured from laminations of materials in the range of soft porous foams to rigid, non-porous films. The rigid, non-porous thermoplastic shells of these bilaminate dental appliances enclose and support an inner layer of soft porous foam.

[0195] A fourth type of dental tray replaces rigid custom dental appliances with disposable U-shaped soft foam trays, which can be individually packaged, and which can be saturated with a pre-measured amount of the composition of the present invention. The soft foam material is generally an open cell plastic material. Such a device is commercially available from Cadco Dental Products in Oxnard, California, USA under the tradename VitalWhite™. Such soft foam trays may comprise a support material (e.g., a closed cell plastic support material) to minimize elution of the whitening agent from the device into the oral cavity to minimize patient ingestion and /or irritation of the tissues of the oral cavity. Alternatively, the soft foam tray is enclosed by a flexible non-porous polymer or the open cell foam is attached to the front inner wall of the dental appliance and/or the open cell foam is attached to the rear inner wall of the dental appliance. Those skilled in the art will readily recognize and understand that the present compositions need to be thick enough not to simply run through the open cell structure of the foam and need to be thin enough to pass slowly through the open cell foam over time. In other words, the open cell foam material has an internal structural spacing dimensioned in relation to the viscosity of the compositions to absorb and allow the composition to pass through.

[0196] An example of a closed cell material is a closed cell polyolefin foam sold by the Voltek division of Sekisui America Corporation of Lawrence, Mass., USA, under the trade name Volora, which is 0.079375 cm to 0.3175 cm (1/32" to 1/8") thick. A closed cell material may also comprise a flexible polymeric material. An example of an open cell material is an open cell polyethylene foam sold by the Sentinel Foam Products division of Packaging Industries Group, Inc. from Hyannis, Mass., USA, under the tradename Opcell, which is 1/16" to 3/8") thick. Other open cell foams useful in the present invention include hydrophilic open foam materials such as hydrogel polymers (for example, Medicell™ foam available from Hydromer, Inc., Branchburg, N.J., USA). The open cell foam may also be a hydrophilic open foam material soaked with agents to impart high fluid absorption, such as polyurethane or polyvinylpyrrolidone chemically soaked with various agents. Preparation of the present multi-phase oral compositions

[0197] Primarily, the preparation of emulsions is well known in the art and any suitable manufacturing process can be used to make the multi-phase oral compositions which can be in the form of an emulsion; see, for example, "Remington: the Science and Practice of Pharmacy", 19th edition, volume II, chapters 20, 80, 86, etc. Generally speaking, the components are separated into those that are oil soluble and those that are water soluble. These are dissolved in their respective solvents by heating, if necessary. The two phases are then mixed and the product is stirred and cooled. After combining the phases, the present multi-phase buccal compositions can be stirred or sheared by various methods, including agitation, intermittent agitation, high-shear mixing, or with the use of high-speed mixers, mixers, colloidal mills, homogenizers, or ultrasonic techniques. Various test methods are available to confirm the type of multiphase oral compositions that have been prepared. These test methods include the dilution test, conductivity test, microscopy and dye solubility test methods. A further description of test methods is disclosed in "Remington: The Science and Practice of Pharmacy", 19th edition, volume 1, 1995, pages 282 to 283.

[0198] In certain embodiments, the multi-phase oral compositions, as disclosed herein, may be produced as follows: dissolving the whitening active in the aqueous phase; then combine the aqueous phase and hydrophobic phase in a mixing vessel and mix well by any means known in the art, for example, a Speedmixer mixer (available from Flactek Inc., Landrum, SC, USA) can be used to preparing the multiphase oral compositions of the present invention. The SpeedMixer™ series mixing procedure is based on double rotation of the mixing vessel using a double asymmetrical centrifugal mix. This combination of centrifugal forces acting on different levels makes it possible to mix the entire container very quickly. Optionally, the composition can be heated, if necessary, to facilitate solution of the lightening active or mixture. Continue mixing the composition until uniformity is achieved. When the active ingredient is included in solid particulate form, the addition of an optional viscosity modifier, such as silica, may be adequate to keep the particulate dispersed and suspended in the composition. Flavorings or sweeteners may also be added to one of the phases of the composition, as desired. Thereafter, the composition can be added to the application support as desired. Examples of multi-phase oral composition formulation

[0199] The following non-limiting Formulation Examples describe, in more detail, the embodiments within the scope of the present invention. Many variations of these Examples are possible without departing from the scope of the invention. Examples of formulation I

RAZÃO* 400 500 667 1000 2000 3500 34483 RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição Grau ultra cosmético, disponível junto à Solvay, Houston, Texas, EUA Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA Exemplos de formulação II[0200] Formulation Examples I can be made using any suitable procedure disclosed above and formulated with a 35% aqueous hydrogen peroxide solution. These Examples illustrate compositions that can be made with 1) the concentration of H2O2 in the total composition in the range of 0.001% to 0.0875%, and 2) the ratio between the concentration of H2O2 in weight percent of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition in the range of 400 to 34,483.

RATIO* 400 500 667 1000 2000 3500 34483 RATIO between the concentration in weight percentage of H2O2 present in the aqueous phase and the concentration in weight percentage of H2O2 present in the total composition Ultra cosmetic grade, available from Solvay, Houston, Texas, USA Grade G-2191, available from Sonneborn, LLC., Parsippany, NJ, USA Formulation Examples II

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 17 Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA Exemplos de formulação III[0201] Formulation Examples IV can be made using any suitable procedure disclosed above and formulated with a 50% aqueous hydrogen peroxide solution. These Examples illustrate compositions that can be made with 1) the concentration of H2O2 in the total composition in the range of 0.0015% to 0.1%, and 2) the ratio of the concentration of H2O2 to percent by weight of H2O2 present in the phase and the concentration in percentage by weight of H2O2 present in the total composition in the range of 500 to 34,483.

* RATIO between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition 17 Grade G-2191, available from Sonneborn, LLC., Parsippany, NJ, USA Examples of formulation III

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 18 Grau ultra cosmético, disponível junto à Solvay (Houston, Texas, EUA) diluído com água 19 Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA Exemplos de formulação IV[0202] Formulation Examples III can be made using any suitable procedure disclosed above and formulated with a 17.5% aqueous hydrogen peroxide solution. These examples illustrate compositions that can be made with 1) the concentration of H2O2 in the total composition in the range of 0.0088% to 0.0875%, and 2) the ratio of the concentration of H2O2 in percent by weight of H2O2 present in the phase aqueous solution and the concentration in weight percentage of H2O2 present in the total composition in the range of 200 to 2,000.

* RATIO between the concentration in percent by weight of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition 18 Grade ultra cosmetic, available from Solvay (Houston, Texas, USA) diluted with water 19 Grade G-2191, available from Sonneborn, LLC., Parsippany, NJ, USA Formulation Examples IV

RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 20 Grau ultra cosmético, disponível junto à Solvay (Houston, Texas, EUA) diluído com água 21 Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA Exemplos de formulação V[0203] Formulation Examples IV can be made using any suitable procedure disclosed above and formulated with an 8.75% aqueous hydrogen peroxide solution. These examples illustrate compositions that can be made with 1) the concentration of H 2 O 2 in the total composition in the range of 0.0044% to 0.099995%; and 2) the ratio between the concentration in percent by weight of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition in the range from 87.5 to 2000.

RATIO between the concentration in percent by weight of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition 20 Grade ultra cosmetic, available from Solvay (Houston, Texas, USA) diluted with water 21 Grade G -2191, available from Sonneborn, LLC., Parsippany, NJ, USA Formulation Examples V

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 22 Grau ultra cosmético, disponível junto à Solvay, Houston, Texas, EUA 23 Grau G-2191, disponível junto à Sonneborn LLC., Parsippany, NJ, EUA 24 Grau Kaydol, disponível junto à Sonneborn LLC., Parsippany, NJ, EUA 25 Grau 400, disponível junto à Baker Hughes, Houston, TX, EUA, dissolvido em óleo mineral a 95 °C 26 Grau W835, disponível junto à Sonneborn LLC., Parsippany, NJ, EUA dissolvido em óleo mineral a 95 °C 27 Grau 400, disponível junto à Baker-Hughes, Houston, TX, EUA, adicionado na composição bucal de múltiplas fases abaixo de seu ponto de fusão de modo que esteja presente como carga particulada 28 Tospearl disponível junto à Momentive Inc. adicionado na composição bucal de múltiplas fases de modo que ele esteja presente como uma carga particulada Exemplos comparativos de formulação Exemplos comparativos de formulação I[0204] Formulation Examples V can be made using any suitable procedure disclosed above and formulated with a 35% aqueous hydrogen peroxide solution. These Examples illustrate compositions that can be made with 1) various hydrophobic phases; and 2) multiple loads.

* RATIO between the concentration in weight percent of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition 22 Grade Ultra Cosmetic, available from Solvay, Houston, Texas, USA 23 Grade G-2191, available from Sonneborn LLC., Parsippany, NJ, USA 24 Grade Kaydol, available from Sonneborn LLC., Parsippany, NJ, USA 25 Grade 400, available from Baker Hughes, Houston, TX, USA, dissolved in mineral oil at 95 °C 26 Grade W835, available from Sonneborn LLC., Parsippany, NJ, USA dissolved in mineral oil at 95 °C 27 Grade 400, available from Baker-Hughes, Houston, TX, USA, added in multi-phase buccal composition below its melting point so that it is present as particulate filler 28 Tospearl available from Momentive Inc. added to the multi-phase buccal composition so that it is present as a particulate filler Comparative Formulation Examples Comparative Formulation Examples I

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 29 Grau ultra cosmético, disponível junto à Solvay, Houston, Texas, EUA 30 Grau Kaydol, disponível junto à Sonneborn LLC., Parsippany, NJ, EUA 31 dioctil sulfosuccinato de sódio, disponível junto à Cytec Industries Inc., NJ, EUA 32 mono-oleato de sorbitan etoxilado, disponível junto ao Spectrum Chemical MfG Group 33 disponível junto ao Calumet Lubricants 34 Álcool cetearílico e cetearet-20, disponíveis junto à Lipo Chemical. Exemplos comparativos de formulação II[0205] Comparative Examples of formulation I can be made using any procedure disclosed above or in EP 1 696 866 B1. These Examples illustrate compositions that 1) have H2O2 contents much higher than 0.1% of the total composition, and 2) have ratios between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition lower than the preferred ranges, according to the present invention.

* RATIO between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition 29 Grade Ultra Cosmetic, available from Solvay, Houston, Texas, USA 30 Grade Kaydol, available from to Sonneborn LLC., Parsippany, NJ, USA 31 Sodium dioctyl sulfosuccinate, available from Cytec Industries Inc., NJ, USA 32 Ethoxylated sorbitan monooleate, available from Spectrum Chemical MfG Group 33 available from Calumet Lubricants 34 Alcohol cetearyl and cetearet-20, available from Lipo Chemical. Comparative Examples of Formulation II

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 35 Grau ultra cosmético, disponível junto à Solvay, Houston, Texas, EUA 36 Grau Kaydol, disponível junto à Sonneborn LLC., Parsippany, NJ, EUA 37 dioctil sulfosuccinato de sódio, disponível junto à Cytec Industries Inc., NJ, EUA 38 mono-oleato de sorbitan etoxilado, disponível junto ao Spectrum Chemical MfG Group[0206]Comparative Examples of formulation II can be made using any procedure disclosed above or in EP 1 696 866 B1. These Examples illustrate compositions that 1) have H2O2 contents much higher than 0.1% of the total composition, and 2) have ratios between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition lower than the preferred ranges, according to the present invention.

* RATIO between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition 35 Grade Ultra Cosmetic, available from Solvay, Houston, Texas, USA 36 Grade Kaydol, available from to Sonneborn LLC., Parsippany, NJ, USA 37 Sodium dioctyl sulfosuccinate, available from Cytec Industries Inc., NJ, USA 38 Ethoxylated sorbitan monooleate, available from Spectrum Chemical MfG Group

[0207] The ratio between the concentration in percentage by weight of the bleaching agent present in the aqueous phase and the concentration in percentage by weight of the bleaching agent present in the total composition of Comparative Examples of formulation I and II is in the range of a minimum of 3.13 to a maximum of 17.64, while the ratio ranges from about 50 to about 34,483 in Examples I, II and III, and in Formulation Examples I, II, III, IV and V above. Specifically, the ratio of the weight percent concentration of the bleaching agent present in the aqueous phase to the weight percent concentration of the bleaching agent present in the total composition of Comparative Formulation Examples I and II has a maximum value of 17.64 while the ratio for Examples I, II and III and Formulation Examples I, II, III, IV, and V above has a minimum of about 50. Methods of using the compositions and/or delivery systems

[0208] The present invention can be applied to a consumer's teeth in the dentist's office by a dental professional, or can be used at home by the consumer. In general, the recommended treatment period is a sufficient period of time to achieve bleaching.

[0209] In the practice of the present invention, the user applies the composition of the present invention that contains the whitening agent to achieve the desired effect, for example, whitening, to one or more teeth. The composition can be applied with a brush applicator, a syringe or a unit dose syringe, squeezable tube, a brush, an applicator pen or brush, a diagonal tip applicator, cotton swab, lip gloss applicator, tape that is removed after application, a tray that is removed after application, or the like, or even with your fingers. The composition may also be combined with an application support, such as a tape of material, a dental tray, or a sponge material, and subsequently applied to the teeth. In certain embodiments, the compositions or delivery systems of the present invention are barely noticeable when applied to teeth. After a desired period of time has elapsed, any residual composition can be easily removed by rubbing, brushing or rinsing the buccal surface.

[0210] In general, it is not necessary to prepare the teeth before applying the present composition. For example, the user may choose to brush the teeth or rinse the mouth before applying the compositions of the present invention, but the surfaces of the oral cavity need not be clean, dry or excessively wet with saliva or water prior to application. However, it is believed that adhesion to tooth enamel surfaces will be improved if teeth are dry prior to application.

[0211]The dental tray appliances can be used as follows. The patient or dentist dispenses the present composition into a soft or rigid dental appliance, and then the participant places the appliance over the dental arch (or fits the device around their teeth to hold the tray in position). Generally speaking, the recommended treatment period is a period of time sufficient to achieve bleaching, as disclosed above. At the end of the treatment period, the dental appliance is removed, cleaned with water to remove any remaining composition, and then stored until the next application.

[0212]The compositions and delivery systems described above can be combined in a kit comprising: 1. the present composition and 2. instructions for use; or comprising: 1. the present composition, 2. instructions for use, and 3. an application support. Furthermore, if the tooth is irradiated by electromagnetic radiation, the kit may additionally comprise a source of electromagnetic radiation of the appropriate wavelength and instructions for use, so that the kit can be used by consumers in a convenient manner. Optional electromagnetic radiation treatment

[0213] The multi-phase oral composition disclosed herein can be used to whiten teeth and/or remove stains from dental surfaces. Furthermore, bleaching effectiveness can be further increased by directing electromagnetic radiation of a suitable wavelength towards at least one tooth. A suitable device for delivering such electromagnetic radiation is shown in Figure 7. A suitable wavelength can be any wavelength, which corresponds to a maximum absorption range of the tooth and/or stain of the tooth to be whitened. For example, the multi-phase buccal composition can be irradiated with electromagnetic radiation having one or more wavelengths in the range from about 200 nm to about 1200 nm. Electromagnetic radiation can be directed at at least one tooth. Also, more than one tooth can be irradiated. In particular, electromagnetic radiation can have a peak intensity at a wavelength in the range of about 400, 405, 410, 415, 420, 425, 430, 435, 440, or 445, 446 nm at about 450, 455, 460, 465, 470, 475, 480, 481, 485, 490, 495, or 500 nm or any other numerical range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. In certain embodiments, electromagnetic radiation has a peak intensity at a wavelength in the range from about 425 nm to about 475 nm, from about 445 nm to about 465 nm, or where the wavelength of intensity peak of electromagnetic radiation is similar to the wavelength at which the spot absorbs most of the electromagnetic radiation. Electromagnetic radiation can be directed to at least one tooth during the partial or total use time of the composition; or after the composition has been removed from the tooth. Electromagnetic radiation may be applied for at least a period of time sufficient for bleaching, for example, for at least about 1 minute, for at least about 5 minutes, or for at least about 10 minutes. Electromagnetic radiation can be applied using the procedure disclosed in US 2013/0295525. Preferably, the multi-phase buccal composition disclosed herein is applied to at least one tooth and held on at least one tooth for a first period of time; After the first period of time, electromagnetic radiation is directed towards the at least one tooth during a second period of time, the first period of time having a duration greater than 50%, preferably 80% of a total duration of the tooth. first and second time period; and finally, the multiphase buccal composition is removed from the at least one tooth.

[0214] Suitable sources of electromagnetic radiation include the source described herein in the section entitled "Clinical Protocol".

[0215] The multiphase oral compositions disclosed herein may be transparent or translucent to electromagnetic radiation with wavelengths from about 400 nm to about 500 nm. In certain embodiments, the multi-phase oral compositions disclosed herein, when applied at a thickness of about 0.0001, 0.001, or 0.01 cm to about 0.01, 0.1, or 0.5 cm in thickness allow about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%, 80%, 90%, or 100% of the electromagnetic radiation from about 400 nm to about 500 nm through them, as measured by a spectrophotometer. In certain embodiments, when a multi-phase buccal composition is applied at a thickness of about 0.1 cm, from about 80% to about 100% of electromagnetic radiation from about 400 nm to about 500 nm passes through it, as measured by a spectrophotometer. The multi-phase oral compositions disclosed herein may, when applied in an amount of from about 0.0001, 0.001 or 0.01 grams to about 0.01, 0.1, 1 or 5 grams, in an application support or tray with a surface area of about 5 cm2 to about 20 cm2, allow about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%, 80%, 90%, or 100% of electromagnetic radiation from about 400 nm to about 500 nm passes through.

[0216] The electromagnetic radiation incident on the tooth surface or the external surface of the support, which can be a tape, in the wavelength range from about 400 to about 500 nm can vary in intensity from about 5, 10 , 25, 50, 75, or 100 mW/cm2 to about 500, 250, 225, 205, 200, 175, 150, 125, 100, 75, 50, 25, 10, or 5 mW/cm2 or any other range which is narrower and which is contained in such a wider numerical range, as if such narrower numerical ranges were expressly written in the present invention. Procedure for measuring the intensity of electromagnetic radiation

[0217]The intensity of electromagnetic radiation can be measured using a spectrometer (USB 2000+ available from Ocean Optics) connected to a 200 micron UV-VIS fiber optic cable with a cosine corrector at the tip (OP 200 -2-UV-VIS available from Ocean Optics). The spectrometer is connected to a computer running the spectrometer software (Oceanview 1.3.4 available from Ocean Optics). The end of the fiber optic cable is kept pointing towards the light source at the location where the light intensity is to be measured. Photons collected on the detector surface are guided through the fiber optic cable to the charge-coupled device in the spectrometer (CCD). The CCD counts the photons that arrive at it during a predetermined period of time at each wavelength from 200 nm to 1100 nm, and uses a software algorithm to convert these photon counts into spectral irradiance (mW/cm2/nm). The spectral irradiance is integrated from 200 nm to 1100 nm by the software to produce the absolute irradiance (mW/cm2), which is the intensity of electromagnetic radiation from 200 nm to 1100 nm. The spectral irradiance is integrated from 400 nm to 500 nm by the software to produce the absolute irradiance (mW/cm2), which is the intensity of electromagnetic radiation from 400 nm to 500 nm.

[0218]For consumer convenience, the multi-phase mouthwash composition disclosed herein may be supplied as a kit comprising the whitening composition disclosed herein, an application holder for easier application, an electromagnetic radiation source that emits electromagnetic radiation in a appropriate wavelength, and instructions for use.

[0219] The compositions of this invention are useful for application to both humans and other animals (e.g., pets, zoo, or domestic animals).

Examples

[0220] The following non-limiting Examples describe, in more detail, preferred embodiments within the scope of the present invention. Many variations of these Examples are possible without departing from the scope of the invention. All Examples were performed at room temperature (RT) and atmospheric pressure, unless otherwise specified.

[0221]These multi-phase oral compositions were made as described above or below.

[0222]Specifically, 500 gram batches of Example I-A and B, of Example II-A, B, and C, of Comparative Example I, and of Example III, A, B, C, and D were prepared by weighing the aqueous solution of hydrogen peroxide (H2O2) and petrolatum in a Speedmixer container ("Max 300 Long Cup Translucent", item number 501 218t available from Flacktek Inc., Landrum, SC, USA), and mixing in a Speedmixer at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes. The walls of the container were then scraped with a plastic spatula, and the contents were mixed a second time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes. The walls of the container were then scraped with a plastic spatula, and the contents mixed a third time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes.

[0223] In addition, a 500 gram batch of Example III E was made by first weighing polyethylene and mineral oil in a Speedmixer container ("Max 300 Long Cup Translucent", item number 501 218t available from Flacktek Inc. , Landrum, SC, USA), heating it in an oven set to 95 °C for about 3 hours, mixing with a spatula for about 30 seconds, followed by mixing in a Speedmixer at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes and cooling overnight at room temperature. Then the aqueous H2O2 solution was added and mixed in a Speedmixer at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes. The walls of the container were then scraped with a plastic spatula, and the contents were mixed a second time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes. The walls of the container were then scraped with a plastic spatula, and the contents mixed a third time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes.

[0224] In addition, a 500 gram batch of Example III F was made by first weighing microcrystalline wax and mineral oil in a Speedmixer container ("Max 300 Long Cup Translucent", item number 501 218t available from Flacktek Inc. ., Landrum, SC, USA), heating them in an oven set to 95 °C for about 3 hours, mixing with a spatula for about 30 seconds, followed by mixing in a Speedmixer at 800 RPM for 30 seconds and cooling overnight at room temperature. Then the aqueous H2O2 solution was added and mixed in a Speedmixer at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes. The walls of the container were then scraped with a plastic spatula, and the contents were mixed a second time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes. The walls of the container were then scraped with a plastic spatula, and the contents mixed a third time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds and 1950 RPM for 2 minutes.

[0225] In addition, a batch of Example IV-A was made as follows: 242.6 g of petrolatum and 7.2 g of 35% aqueous hydrogen peroxide were added to a container of Speedmixer Max 300 Long (Flacktek Inc., Landrum, SC, USA) and mixed in a SpeedMixer DAC 400 FVZ (Flacktek Inc., Landrum, SC, USA) for 30 seconds at 1600 rev/min. The mixture was transferred to an empty 378.5 mL (12.8 oz) Caulk Cartridge (McMaster Carr, Robbinsville, NJ, USA) and stored in a refrigerator until the measured product temperature was 9°C. The Caulk Cartridge was inserted into a pneumatic caulking gun (McMaster Carr, Robbinsville, NJ, USA), and connected to the inlet of a model M-110Y microfluidizer (Microfluidics, Westwood, MA 02090, USA). The microfluidizer outlet tubing was arranged so that the product passed through just one F20Y interaction chamber and several cm of tubing before and after. The inlet pressure to the microfluidizer was set to 290 kPa (42 psig), and the inlet pressure to the Caulk Cartridge cartridge was set to 648 kPa (94 psig). The final product was collected in a plastic container.

[0226] In addition, a batch of Example IV-B was made as follows: 228.8 g of petrolatum and 21.6 g of 35% aqueous hydrogen peroxide were added to a container of Speedmixer Max 300 Long (Flacktek Inc., Landrum, SC, USA) and mixed in a SpeedMixer DAC 400 FVZ (Flacktek Inc., Landrum, SC, USA) for 30 seconds at 1600 rev/min. The mixture was transferred to an empty 379 mL (12.8 oz) Caulk Cartridge (McMaster Carr, Robbinsville, NJ, USA) and stored in a refrigerator until the measured product temperature was 8°C. The Caulk Cartridge was inserted into a pneumatic caulking gun (McMaster Carr, Robbinsville, NJ, USA), and connected to the inlet of a model M-110Y microfluidizer (Microfluidics, Westwood, MA 02090, USA). The microfluidizer outlet tubing was arranged so that the product passed through just one F20Y interaction chamber and several centimeters of tubing before and after. The inlet pressure to the microfluidizer was set to 290 kPa (42 psig), and the inlet pressure to the Caulk Cartridge cartridge was set to 648 kPa (94 psig). The final product was collected in a plastic container.

Example I

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 1 Grau ultra cosmético, disponível junto à Solvay, Houston, Texas, EUA 2 Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA[0227] The multi-phase oral compositions of Example IA and B were made using the procedure described above and formulated with a 35% aqueous solution of hydrogen peroxide. The following parameters were measured in Example IB using the procedures specified herein: a) two-dimensional density of the aqueous phase droplets of the multiphase buccal composition having a cross-sectional area greater than about 10,000 square microns per square centimeter of the two-dimensional plane ; b) standard deviation of the peroxide concentration of the multi-phase buccal composition applied to peroxide test strips; c) average peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips.

* RATIO between the concentration in weight percent of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition 1 Grade Ultra Cosmetic, available from Solvay, Houston, Texas, USA 2 Grade G-2191, available from Sonneborn, LLC., Parsippany, NJ, USA

Example II

RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição 3 Grau ultra cosmético, disponível junto à Solvay (Houston, Texas, EUA) diluído com água 4 Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA[0228] The multi-phase buccal composition of Example II-A was made using the procedure described above and was formulated with a 17.5% aqueous hydrogen peroxide solution. The multi-phase oral compositions of Example II-B and C were made using the procedure described above and formulated with a 5% aqueous hydrogen peroxide solution.

RATIO between the concentration in percent by weight of H2O2 present in the aqueous phase and the concentration in percent by weight of H2O2 present in the total composition 3 Grade ultra cosmetic, available from Solvay (Houston, Texas, USA) diluted with water 4 Grade G -2191, available from Sonneborn, LLC., Parsippany, NJ, USA

Example III

RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na fase aquosa e a concentração em porcentagem em peso de H2O2 presente no total da composição Grau ultra cosmético, disponível junto à Solvay, Texas, EUA Parsippany, NJ, EUA Grau 400, disponível junto à Baker-Hughes, Houston, TX, EUA, dissolvido em óleo mineral a cerca de 95 °C Grau W835, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA, dissolvido em óleo mineral a cerca de 95 °C.[0229] The multi-phase oral compositions of Example III were made using the procedure described above and formulated with 1) a 35% aqueous hydrogen peroxide solution of different chemical grades, as well as 2) different materials used such as hydrophobic phase.

RATIO between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition Ultra Cosmetic Grade, available from Solvay, Texas, USA Parsippany, NJ, USA Grade 400, available from from Baker-Hughes, Houston, TX, USA, dissolved in mineral oil at about 95°C Grade W835, available from Sonneborn, LLC., Parsippany, NJ, USA, dissolved in mineral oil at about 95°C.

Example IV

* RAZÃO entre a concentração em porcentagem em peso de H2O2 presente na H2O2 presente no fase aquosa e a concentração total da composição em porcentagem em peso de 14 Houston, Texas, Grau EUA ultra cosmético, disponível junto à Solvay, 15 Grau Parsippany, NJ, EUA Exemplos G-2218, disponível comparativos junto à Sonneborn , LLC.,[0230] The multi-phase oral compositions of Examples IV-A and B were made using the procedure described above and formulated with a 35% aqueous solution of hydrogen peroxide. The following parameters were measured in Examples IV-A and IV-B using the procedures specified herein: a) two-dimensional density of the aqueous phase droplets of the multiphase buccal composition with a cross-sectional area greater than about 10,000 square micrometers per square centimeter of the two-dimensional plane; b) standard deviation of the peroxide concentration of the multi-phase buccal composition applied to peroxide test strips; c) average peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips.

* RATIO between the weight percent concentration of H2O2 present in the H2O2 present in the aqueous phase and the total weight percent concentration of the composition of 14 Houston, Texas, US Grade Ultra Cosmetic, available from Solvay, 15 Grade Parsippany, NJ, USA Examples G-2218, comparative available from Sonneborn, LLC.,

[0231]All Examples were performed at room temperature (RT) and atmospheric pressure, unless otherwise specified. Comparative example I

14 Grau G-2191, disponível junto à Sonneborn, LLC., Parsippany, NJ, EUA Eficácia de clareamento do exemplo IA em função do exemplo comparativo I[0232] Comparative example I was made using the procedure described above and formulated without bleaching agent.

14 Grade G-2191, available from Sonneborn, LLC., Parsippany, NJ, USA Whitening effectiveness of example IA versus comparative example I

[0233] The bleaching efficacy of Example IA and Comparative Example I were measured in accordance with the clinical protocol as disclosed herein. Specifically, this was a randomized, single-center, two-treatment, parallel-group clinical study conducted in 39 adults who had never had a professional, licensed, or investigational tooth whitening treatment. All participants were at least 18 years of age, had all four measurable maxillary incisors, and had no self-reported tooth sensitivity. Participants were randomly selected for study treatments based on L* and b* color values and age. Participants were assigned to one of two treatment groups: • Example IA (22 participants, mean L* of 74.1 and mean b* of 15.6) or • Comparative Example I (17 participants, mean L* of 74.2 and average b* of 15.2)

[0234] The participants' anterior maxillary teeth were treated with the multi-phase oral composition they were assigned with for 60 minutes once daily with the use of a polyethylene tape as an application support. The polyethylene tapes were 66 mm x 15 mm in size and 0.0178 mm in thickness. 0.6 gram to 0.8 gram of the multiphase buccal composition was applied to each polyethylene strip prior to application to the maxillary anterior teeth.

[0235]The distribution of the assigned maxillary tapes and all applications were supervised by a local clinical team. For each treatment, participants wore a tape with the multi-phase oral composition assigned to them for a total of 60 minutes. After 50 minutes of wearing each tape, a trained hygienist applied electromagnetic radiation towards the facial surfaces of the maxillary anterior teeth for 10 minutes. Electromagnetic radiation was directed to the teeth through the tape and through the multi-phase oral composition. Electromagnetic radiation was applied using the electromagnetic radiation source described herein in the section entitled "Clinical Protocol". The intensity of electromagnetic radiation from 400 nm to 500 nm measured on the central axis of each cone of electromagnetic radiation exiting the exit surface of the transparent window through which electromagnetic radiation passes towards the maxillary anterior teeth was measured to be about from 175 mW/cm2 to about 225 mW/cm2 as measured by the procedure disclosed herein.

[0236]Digital images were collected at baseline (reference), and on the day after the 3rd, 10th and 14th treatments.

[0237]The group using Example IA demonstrated a statistically significant (p<0.0001) incremental reduction in yellowing (-Δb*) at all time points tested relative to the baseline; in addition, an increase in luminosity (ΔL*) was observed in this group on the day after the seventh, tenth and fourteenth treatments (p<0.001).

[0238]The group using Comparative Example I did not differ from the reference values after three, seven, and ten applications, and showed a small, statistically significant (p=0.0007) decrease in yellowing (-Δb*) after fourteen treatments; no change in brightness (ΔL*) was detected.

[0239] In addition, the group in Example IA demonstrated a greater decrease in yellowing (-Δb*) compared to the group in Comparative Example I at all time points tested. Table I shows the results in detail:

[0240] These results clearly demonstrate the surprisingly high effectiveness of Example IA (applied to a tape and used with electromagnetic radiation, as disclosed herein) even though it has less than 0.1% H2O2.

[0241] The ratio of the bleaching effectiveness of Example IA (applied to a tape and used with electromagnetic radiation as disclosed herein), as measured in accordance with the clinical protocol as disclosed herein, and calculated as -Δb*, and the percentage in weight of whitening agent present in the total multi-phase oral composition was 6.07, 14.5, 17.0 and 19.5 after 3, 7, 10 and 14 treatments, respectively.

[0242] These results also clearly demonstrate the surprisingly high effectiveness of Example IA (applied on a tape and used with electromagnetic radiation, as disclosed herein) over Comparative Example I (applied on the same tape and used with the same source of electromagnetic radiation ).

[0243] Figure 7 shows example images of teeth treated with the multi-stage whitening oral composition of Example IA. The RGB images were converted to black and white images. Images were obtained before and after 14 treatments with the multi-phase buccal composition of Example IA. Three teeth were shown, with the left side of the tooth showing its visual reference appearance and the right side of the tooth showing its visual appearance after 14 treatments. It can be clearly seen that treatment with the multi-phase buccal composition of Example IA visibly whitens the tooth surface. All three teeth appear whiter on the right side compared to the left side.

[0244] It is also surprising that none of the study participants reported tooth sensitivity despite experiencing the high effectiveness of Example IA (applied to a tape and used with a source of electromagnetic radiation, as disclosed herein).

Comparative example II

[0245] Comparative Example II is a tooth whitening tape product commercially available as Crest Whitestrips with 5.25% H2O2 (available from Procter & Gamble, Cincinnati, OH, USA). It is an aqueous gel containing 5.25% hydrogen peroxide (H2O2); and since it is an aqueous gel, the ratio between the weight percent concentration of H2O2 present in the aqueous phase and the weight percent concentration of H2O2 present in the total composition is 1. Whitening effectiveness of comparative example II (Gel aqueous with 5.25% H2O2)

[0246] The whitening efficacy of a second comparative composition (Comparative Example II - product on whitening strips designated Crest Whitestrips with 5.25% H2O2) containing a final concentration of 5.25% H2O2 in an aqueous gel was measured in a clinical study. Specifically, the study for Comparative Example II was a single-center controlled clinical trial. The target population was adult participants with no history of teeth whitening. Participants were treated with the above comparative aqueous gel, with 5.25% H2O2 (Comparative Example II) supplied on a polyethylene tape. The group (20 participants, mean L* of 72.8 and mean b* of 16.4) wore the tape for 60 minutes once a day for 14 days.

[0247]Digital images were obtained at baseline (reference), and on the day after the 7th and 14th treatments. The results of the group using Comparative Example II (5.25% H2O2 aqueous gel) applied to a tape for 60 minutes (same time period as Example IA in the clinical trial described above) are shown in the Table below. Table II shows the results in detail:

[0248] After 7 treatments, Comparative Example II (aqueous gel with 5.25% H2O2 applied to a tape for 60 minutes) produced an average change in yellowing of -0.985 while Example IA (also applied to a tape and used with a source of electromagnetic radiation) provided an average change in yellowing of -1.45 despite having a H2O2 concentration approximately 5250% lower than the aqueous gel (0.1% H2O2 versus 5.25% H2O2) used in the Comparative Example II. Similarly, after 14 treatments, Comparative Example II produced an average change in yellowing of -1.43 while Example IA gave an average change in yellowing of -1.95 even though it had an H2O2 concentration approximately 5250% lower than the aqueous gel (0.1% H2O2 versus 5.25% H2O2). It is worth noting in Table I, that Comparative Example I, which had the same source of electromagnetic radiation disclosed here, but with 0.0% H2O2, provided an average change in yellowing of only 0.005 and -0.408 after 7 and 14 treatments respectively. These results clearly also demonstrate the surprisingly high effectiveness of Example IA (applied to a tape and used with a source of electromagnetic radiation, as disclosed herein) even though it had an approximately 5250% lower H2O2 concentration than the comparative aqueous gel (0.1 % H2O2 versus 5.25% H2O2) used in Comparative Example II.

[0249]Furthermore, it is worth noting that the ratio between the weight percentage concentration of the bleaching agent present in the aqueous phase and the weight percentage concentration of the bleaching agent present in the total composition of Comparative Example II is 1, while Example IA has a ratio of 350.02.

[0250] The ratio of the whitening effectiveness of Comparative Example I, measured according to the clinical protocol disclosed herein, and calculated as -Δb* and the weight percentage of the whitening agent present in the total multi-phase oral composition was 0.19 and 0.27 after 7 and 14 treatments, respectively. This is less than the ratio of the bleaching effectiveness of Example IA (applied to a tape and used with an electromagnetic radiation source, as disclosed herein), measured in accordance with the clinical protocol disclosed herein, and calculated as -Δb* and the weight percentage of whitening agent present in the total multi-phase oral composition which was measured to be 14.5 and 19.5 after 7 and 14 treatments, respectively. Example IB whitening effectiveness

[0251] The bleaching efficacy of Example IB was measured according to the clinical protocol as disclosed herein. Specifically, this was a single-treatment, single-center clinical study conducted in 8 adults who had never had a professional, licensed, or investigational tooth whitening treatment. All participants were at least 18 years of age, had all four measurable maxillary incisors, and had no self-reported tooth sensitivity. Participants were assigned to the following treatment group: • Example IB (8 participants, mean L* of 73,248 and mean b* of 16,368)

[0252] Participants' anterior maxillary teeth were treated with the multi-phase buccal composition of Example IB for 60 minutes once daily, using a polyethylene tape as an application support for three days. The polyethylene tapes were 66 mm x 15 mm in size and 0.0178 mm in thickness. 0.6 gram to 0.8 gram of the buccal composition was applied to each polyethylene strip prior to application to the maxillary anterior teeth.

[0253]The distribution of the maxillary tapes and all applications were carried out by a local clinical team. Participants wore a multi-phase oral composition tape for a total of 60 minutes per treatment for three days. After 50 minutes of wearing each tape, a trained hygienist applied electromagnetic radiation towards the facial surfaces of the maxillary anterior teeth for 10 minutes. Electromagnetic radiation was directed to the teeth through the tape and through the multi-phase oral composition. Electromagnetic radiation was applied using the electromagnetic radiation source described herein in the section entitled "Clinical Protocol". The intensity of electromagnetic radiation from 400 nm to 500 nm measured on the central axis of each cone of electromagnetic radiation exiting the exit surface of the transparent window through which electromagnetic radiation passes towards the maxillary anterior teeth was measured to be about from 175 mW/cm2 to about 225 mW/cm2 as measured by the procedure disclosed herein.

[0254]Digital images were collected before tapes were applied on Day 1 (reference), Day 2 and Day 3; and after the tapes were removed on Day 1, Day 2 and Day 3.

[0255]Participants demonstrated a statistically significant (p<0.0001) reduction in yellowing (-Δb*) at all time points tested relative to the reference level. Table III shows the results in detail:

[0256] These results clearly demonstrate the surprisingly high effectiveness of Example IB (applied to a tape and used with electromagnetic radiation, as disclosed herein) even though it has less than 1% H2O2. This is even more surprising as this high efficacy was provided after only 1, 2 or 3 treatments. Furthermore, despite the high efficacy, surprisingly only 12.5% of participants reported tooth sensitivity and even then, it was characterized as moderate.

[0257] It is worth noting from Table II that even after 7 treatments, Comparative Example II (aqueous gel with 5.25% H2O2 applied on a strip for 60 minutes) produced an average change in yellowing of only -0.985, while Example IB (also applied to a tape and used with a source of electromagnetic radiation) provided an average change in yellowing of -2.931 after only 3 treatments, despite having a H2O2 concentration approximately 525% lower than the aqueous gel (0.99995 % H2O2 versus 5.25% H2O2) used in Comparative Example II. It is also worth noting from Table I that even after 7 treatments, Comparative Example I, which had the same source of electromagnetic radiation disclosed here, but with 0.0% H2O2, provided an average change in yellowing of only 0.005 while Example IB (also applied to a tape, and used with the same source of electromagnetic radiation) provided an average change in yellowing of -2.931 after only 3 treatments. This further highlights the surprisingly high effectiveness of Example IB. Whitening Efficacy of Examples IV-A and IV-B

[0258] The whitening efficacy of Examples IV-A and IV-B was measured in accordance with the clinical protocol as disclosed herein. Specifically, this was a randomly selected, single-center, two-treatment, parallel-group clinical study of 23 adults who had never had a professional, licensed, or investigational tooth whitening treatment. All participants were at least 18 years of age, had all four measurable maxillary incisors, and had no self-reported tooth sensitivity. Participants were randomly selected for study treatments based on L* and b* color values and age. Participants were assigned to one of two treatment groups: • Example IV-A (11 participants, mean L* of 70,342 and mean b* of 16,669) or • Example IV-B (12 participants, mean L* of 72,146 and mean b* of 17,170)

[0259] Participants' anterior maxillary teeth were treated with the designated multi-phase oral composition for 60 minutes once daily, using a polyethylene tape as an application support for three days. The polyethylene tapes were 66 mm x 15 mm in size and 0.0178 mm in thickness. 0.6 gram to 0.8 gram of the buccal composition was applied to each polyethylene strip prior to application to the maxillary anterior teeth.

[0260] The distribution of the maxillary tapes and all applications were made by a local clinical team. Participants wore a tape with the multi-phase oral composition for a total of 60 minutes per day for three days. After 50 minutes of wearing each tape, a trained hygienist applied electromagnetic radiation towards the facial surfaces of the maxillary anterior teeth for 10 minutes. Electromagnetic radiation was directed to the teeth through the tape and through the multi-phase oral composition. Electromagnetic radiation was applied using the electromagnetic radiation source described herein in the section entitled "Clinical Protocol". The intensity of electromagnetic radiation from 400 nm to 500 nm measured on the central axis of each cone of electromagnetic radiation exiting the exit surface of the transparent window through which electromagnetic radiation passes towards the maxillary anterior teeth was measured to be about from 175 mW/cm2 to about 225 mW/cm2 as measured by the procedure disclosed herein.

[0261]Digital images were collected before tapes were applied on Day 1 (reference), Day 2 and Day 3; and after the tapes were removed on Day 1, Day 2 and Day 3.

[0262]Participants demonstrated a statistically significant (p<0.0001) reduction in yellowing (-Δb*) at all time points tested relative to the reference level. Table IV shows the results in detail:

[0263] These results clearly demonstrate the surprisingly high efficacy and low level of oral irritation and tooth sensitivity of Examples IV-A (supplied on a tape and used with electromagnetic radiation, as disclosed herein). This is even more surprising as this high efficacy was provided after only 1, 2 or 3 treatments, even with only 0.99995% H2O2.

[0264]As before, it is worth noting from Table II that even after 7 treatments, Comparative Example II (aqueous gel with 5.25% H2O2 applied to a tape for 60 minutes) produced an average change in yellowing of only -0.985 while Example IV-A (also applied to a tape and used with an electromagnetic radiation source) provided an average change in yellowing of -2.086 after just 3 treatments, even though it had a H2O2 concentration approximately 525% lower than the gel. aqueous (0.99995% H2O2 versus 5.25% H2O2) used in Comparative Example II. It is also worth noting from Table I that even after 7 treatments, Comparative Example I, which had the same source of electromagnetic radiation disclosed here, but with 0.0% H2O2, provided an average change in yellowing of only 0.005 while Example IV -A (also applied to a tape, and used with the same source of electromagnetic radiation) provided an average change in yellowing of -2.086 after just 3 treatments. This further highlights the surprisingly high effectiveness of Example IV-A.

[0265]Combining the observation that: 1) Example I-B provided an average decrease in yellowing (-Δb*) of 2.931 after three treatments, while Example IV-A provided an average decrease in yellowing (-Δb*) of 2.086 after three treatments with the observation that; 2) the average peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips measured using the procedure specified in the present invention is also higher for Example I-B relative to IVA (47.55 versus 14.87) , despite the fact that both Examples have the same H2O2 content (about 0.99995%), shows that the bleaching effectiveness, measured by the mean decrease in yellowing (-Δb*), increases with the mean peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips measured using the procedure specified herein, increases.

[0266] In addition, despite the high efficacy of Example IV-A, surprisingly only 9.1% of participants reported or were observed to have mouth irritation, 0% of participants reported tooth sensitivity, and only 9.1% of participants were observed to have with mouth irritation or tooth sensitivity which were possibly or probably related to the product and even in these cases it was characterized as moderate.

[0267]Combining the observation that: 1) only 9.1% of participants reported or were observed to experience mouth irritation and 0% of participants reported tooth sensitivity when treated with Example IV-A, while 37.5% of participants reported or were observed to have mouth irritation and 12.5% of participants reported tooth sensitivity when treated with Example I-B with the observation that; 2) the two-dimensional density of aqueous phase droplets with a cross-sectional area greater than 10,000 square micrometers per square centimeter of the two-dimensional plane measured using the procedure specified herein was also lower for Example IV-A than for Example I-B (0.1 versus 10.3) despite both Examples having the same H2O2 content (about 0.99995%), it shows that oral irritation and tooth sensitivity decrease with the two-dimensional density of aqueous phase droplets with a cross-sectional area greater than 10,000 square micrometers per square centimeter of the two-dimensional plane measured using the procedure specified herein, decreases.

[0268]Combining the observation that: 1) only 9.1% of participants reported or were observed to have mouth irritation and no participant (0%) reported tooth sensitivity when treated with Example IV-A while 37.5% of participants reported or were observed to have mouth irritation and 12.5% of participants reported tooth sensitivity when treated with Example I-B with the observation that; 2) the standard deviation of the peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips measured using the procedure specified herein was also lower for Example IV-A relative to I-B (5.15 versus 50.00). 17), despite both Examples having the same H2O2 content (about 0.99995%) shows that oral irritation and tooth sensitivity decrease as the standard deviation of the peroxide concentration of the multiphase oral composition applied to the strips of peroxide test measured using the procedure specified here, decreases.

[0269]Further, combining the observation that: 1) the ratio of bleaching effectiveness to the fraction of participants reporting mouth irritation or who were observed to have mouth irritation was 22.923 for Example IV-A and only 7.816 for Example I-B with the observation that 2) the ratio of the average peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips peroxide was also higher in Example IV-A than in Example I-B (2.89 versus 0.95), although both Examples had the same content of bleaching agent (about 1%), shows that the ratio between whitening effectiveness and the fraction of participants who reported oral irritation or were observed to have oral irritation decreases as the ratio of the average peroxide concentration of the multi-phase oral composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips decreases.

[0270]Combining the observation that: 1) the ratio of bleaching effectiveness to the fraction of participants reporting tooth sensitivity was >100 for Example IV-A and only 23,448 for Example I-B with the observation that; 2) the ratio of the average peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips was also higher in Example IV -A than in Example I-B (2.89 versus 0.95), despite both Examples having the same bleaching agent content (about 1%), shows that the ratio of bleaching effectiveness to the fraction of Participants who reported tooth sensitivity decreased as the ratio of the mean peroxide concentration of the multi-phase oral composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of the multi-phase oral composition applied to the peroxide test strips decreased. .

[0271]Further, combining the observation that: 1) the ratio of bleaching effectiveness to the fraction of participants who reported dental irritation or were observed to have oral irritation was 22.923 for Example IV-A and only 5.862 for Example I-B with the observation that; 2) the ratio of the average peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of the multi-phase buccal composition applied to the peroxide test strips was also higher for the Example IV-A than for Example I-B (2.89 versus 0.95), despite both Examples having the same bleaching agent content (about 1%), shows that the ratio between bleaching effectiveness and The fraction of participants who reported oral irritation or were observed to have oral irritation decreases as the ratio between the mean peroxide concentration of the multi-phase oral composition applied to the peroxide test strips and the standard deviation of the peroxide concentration of the multi-phase oral composition applied to the peroxide test strips decreases.

[0272]The above clinical results also show that Example IV-B provided very high efficacy as measured by the mean decrease in yellowing (-Δb* of 3.204, while having low oral irritation (only 16.7%), sensitivity low tooth sensitivity (only 16.7%) and oral irritation or low tooth sensitivity (only 33.3%).

Comparative example III

[0273] Comparative Example III is a 14% H2O2 tooth whitening tape product (available from Procter & Gamble, Cincinnati, OH, USA). It is an aqueous gel containing 14% hydrogen peroxide (H2O2) Whitening effectiveness of comparative example III (aqueous gel with 14% H2O2)

[0274] The whitening efficacy of a third comparative composition (Comparative Example III - product on whitening strips with 14% H2O2) containing a final concentration of 14% H2O2 in an aqueous gel, was measured as part of five clinical studies many different. Target populations were adult participants with no prior history of teeth whitening. Participants were treated with the above comparative aqueous gel with 14% H2O2 (Comparative Example III) provided on a polyethylene tape. All five separate groups (totaling over 100 participants) wore the tape for 30 minutes twice a day for 21 days.

[0275]Digital images were obtained at baseline (reference) and the day after the 21st treatment. The combined results of all five clinical studies on participants who used Comparative Example III (14% H2O2 aqueous gel) applied on a strip for 30 minutes twice daily for 21 days are shown in the Table below. Table V shows the results in detail:

[0276] Comparative Example III (14% H2O2 aqueous gel applied to a tape for 60 minutes) produced an average change in yellowing of -3.09 while Example IV-B (also applied to a tape and used with a source of electromagnetic radiation) provided an average change in yellowing of -3.204 even though it had an approximately 466% lower H2O2 concentration than the aqueous gel (2.99985% H2O2 versus 14% H2O2) used in Comparative Example III. These results show the surprisingly high efficacy of Example IV-B, especially as it was only treated for 3 days (once a day) while Comparative Example III was treated for 21 days (twice a day).

[0277]In addition, Comparative Example III provided high efficacy (-Δb* of 3.09), but also had high oral irritation (29.6%), high tooth sensitivity (38.3%), and high irritation. mouth or tooth sensitivity (58.3%). In contrast, Example IV-B also provided very high efficacy (-Δb* of -3.204), although showing low oral irritation (only 16.7% low tooth sensitivity (only 16.7%) and low oral irritation or tooth sensitivity (only 33.3%) These clinical results highlight the surprisingly high efficacy combined with the surprisingly low oral irritation and tooth sensitivity of Example IV-B.

[0278] The ratio of whitening efficacy (-Δb*) to the fraction of participants who reported oral irritation or were observed to have oral irritation was 19.186 for Example IV-B and 22.923 for Example IV-A compared to only 10,439 for Comparative Example III. Similarly, the ratio of bleaching efficacy (-Δb*) to the fraction of participants reporting tooth sensitivity was 19.186 for Example IV-B and > 100 for Example IV-A compared to only 8.067 for Example IV-B. Comparative Example III. Similarly, the ratio of bleaching effectiveness (-Δb *) to the fraction of participants who reported tooth sensitivity or mouth irritation or were observed to have oral irritation was 9.622 for Example IV-B and 22.923 for Example IV-A compared to only 5,300 for Comparative Example III. These data highlight the surprisingly high ratio of bleaching efficacy to tooth sensitivity and/or oral irritation provided by Examples IV-B and IV-A.

[0279] The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values mentioned. Instead, unless otherwise specified, each of these dimensions is intended to mean both the mentioned value and a range of functionally equivalent values around that value. For example, a dimension disclosed as "40mm" is intended to mean "about 40mm".

[0280] Each document cited herein, including any cross-referenced or related patent or patent application, and any patent application or patent in which the present application claims priority or benefit therefrom, is hereby incorporated in its entirety by way of title. reference unless expressly excluded or otherwise limited. Mention of any document is not an admission that it constitutes prior art with respect to any invention disclosed or claimed herein, nor that it, by itself or in any combination with any other reference or references, teaches, suggests or discloses such invention. . In addition, if there is a conflict between any meaning or definition of a term mentioned in this document and any meaning or definition of the same term in a document incorporated by reference, the meaning or definition given to that term in this document will take precedence.

[0281] While specific embodiments of the present invention have been illustrated and described, it will be apparent to those skilled in the art that various other changes and modifications may be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that fall within the scope of the present invention.

Claims (15)

1. Kit for whitening teeth, characterized in that it comprises: a) a multi-phase oral composition comprising: i) from 0.002% to 5%, by weight of the multi-phase oral composition, of an aqueous phase having a whitening agent; ii) a hydrophobic phase; and b) a source of electromagnetic radiation capable of directing electromagnetic radiation with one or more wavelengths in the range of 200 nm to 1,700 nm towards at least one tooth; wherein the multi-phase buccal composition is a water-in-oil emulsion; wherein the concentration of the whitening agent is up to 0.1% by weight of the multi-phase buccal composition; wherein the hydrophobic phase is a predominant portion of the multiphase buccal composition. 2. Kit according to claim 1, characterized in that the amount of the whitening agent is in the range of 0.01% to 0.095% by weight of the multi-phase oral composition. 3. Kit, according to claim 1 or 2, characterized in that the ratio between the concentration in percentage by weight of bleaching agent present in the aqueous phase and the concentration in percentage by weight of bleaching agent present in the total of multiphase buccal composition is at least 50. 4. Kit according to any one of claims 1 to 3, characterized in that the value of consistency by cone penetration of the hydrophobic phase or multi-phase buccal composition is from 100 to 300, as measured by the ASTM D937 method -07. 5. Kit according to any one of claims 1 to 4, characterized in that the melting point of the hydrophobic phase droplet is from 40°C to 80°C, as measured by the ASTM D127-08 method. A kit according to any one of claims 1 to 5, characterized in that the two-dimensional density of droplets having a cross-sectional area greater than 10,000 square microns is not greater than 20 per square centimeter. 7. Kit according to any one of the preceding claims, characterized in that the standard deviation of the peroxide concentration of the multi-phase oral composition spread on the peroxide test strips is not greater than 50. 8. Kit according to any one of the preceding claims, characterized in that the average peroxide concentration of the multi-phase oral composition spread on the peroxide test strips is from 1 to 100. 9. Kit according to any one of the preceding claims, characterized in that the average residual concentration of peroxide from the multi-phase oral composition spread on the teeth is 20 to 200. 10. Kit according to any one of the preceding claims, characterized in that the whitening agent in the multi-phase oral composition comprises hydrogen peroxide. 11. Kit according to any of the preceding claims, characterized in that the whitening effectiveness of the multi-phase oral composition calculated as -Δb* and measured according to the clinical protocol, as disclosed herein, is at least 1.5. 12. Kit according to any of the preceding claims, characterized in that the ratio between the whitening effectiveness of the multi-phase oral composition calculated as -Δb* and measured according to the clinical protocol as disclosed herein, and the weight percentage of the whitening agent present in the total multi-phase oral composition is at least 1.5. 13. Kit according to any one of the preceding claims, characterized in that it comprises a delivery carrier. 14. Kit according to claim 13, characterized in that the delivery carrier is a strip. 15. Kit for whitening teeth, according to claim 14, characterized by the fact that the source of electromagnetic radiation emits electromagnetic radiation in the range of 400 nm to 500 nm, colliding with the external surface of the delivery carrier or at least a tooth, in the range of 175 mW/cm2 to 225 mW/cm2.

Images